Kinnate Biopharma Inc. - Annual Report: 2021 (Form 10-K)

☒

ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

☐

TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

Delaware		82-4566526
(State or other jurisdiction of incorporation or organization)		(I.R.S. Employer Identification No.)

103 Montgomery Street, Suite 150 The Presidio of San Francisco San Francisco, CA		94129
(Address of principal executive offices)		(Zip Code)

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.0001 par value per share		KNTE		The Nasdaq Stock Market LLC (The Nasdaq Global Select Market)

Large accelerated filer	☐	Accelerated filer	☐
Non-accelerated filer	☒	Smaller reporting company	☒
Emerging growth company	☒

		Page
PART I
Item 1.	Business	3
Item 1A.	Risk Factors	50
Item 1B.	Unresolved Staff Comments	109
Item 2.	Properties	110
Item 3.	Legal Proceedings	110
Item 4.	Mine Safety Disclosures	110
PART II
Item 5.	Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities	111
Item 6.	[Reserved]	111
Item 7.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	112
Item 7A.	Quantitative and Qualitative Disclosures About Market Risk	122
Item 8.	Financial Statements and Supplementary Data	123
Item 9.	Changes in and Disagreements With Accountants on Accounting and Financial Disclosure	143
Item 9A.	Controls and Procedures	143
Item 9B.	Other Information	144
Item 9C.	Disclosure Regarding Foreign Jurisdictions that Prevent Inspections	144
PART III
Item 10.	Directors, Executive Officers and Corporate Governance	145
Item 11.	Executive Compensation	145
Item 12.	Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters	145
Item 13.	Certain Relationships and Related Transactions, and Director Independence	145
Item 14.	Principal Accounting Fees and Services	145
PART IV
Item 15.	Exhibits, Financial Statement Schedules	145
Item 16	Form 10-K Summary	145
SIGNATURES		148

•

the ability of our ongoing and planned  future preclinical studies and ongoing and planned future clinical trials to demonstrate safety and efficacy of our product candidates, and other positive results;

•

the timing, progress and results of ongoing and planned future preclinical studies and clinical trials for our current product candidates and other product candidates we may develop, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work, the period during which the results of the studies or trials will become available, and our research and development programs;

•

the timing, scope and likelihood of regulatory filings and approvals, including timing of INDs and final FDA approval of our current product candidates and any other future product candidates;

•

the timing, scope or likelihood of foreign regulatory filings and approvals;

•

our ability to develop and advance our current product candidates and programs into, and successfully complete, clinical studies;

•

our manufacturing, commercialization, and marketing capabilities and strategy;

•

our plans relating to commercializing our product candidates, if approved, including the geographic areas of focus and sales strategy;

•

the need to hire additional personnel and our ability to attract and retain such personnel;

•

the size of the market opportunity for our product candidates, including our estimates of the number of patients who suffer from the diseases we are targeting;

•

our expectations regarding the approval and use of our product candidates in combination with other drugs;

•

our competitive position and the success of competing therapies that are or may become available;

•

our estimates of the number of patients that we will enroll in our clinical trials;

•

the beneficial characteristics, and the potential safety, efficacy and therapeutic effects of our product candidates;

•

our ability to obtain and maintain regulatory approval of our product candidates;

•

our plans relating to the further development of our product candidates, including additional indications we may pursue;

•

existing regulations and regulatory developments in the United States, Europe and other jurisdictions;

•

our expectations regarding the impact of the COVID-19 pandemic on our business;

•

our intellectual property position, including the scope of protection we are able to establish and maintain for intellectual property rights covering our current product candidates and other product candidates we may develop, including the extensions of existing patent terms where available, the validity of intellectual property rights held by third parties, and our ability not to infringe, misappropriate or otherwise violate any third-party intellectual property rights;

•

our continued reliance on third parties to conduct additional preclinical studies and planned clinical trials of our product candidates, and for the manufacture of our product candidates for preclinical studies and clinical trials;

•

our ability to obtain, and negotiate favorable terms of, any collaboration, licensing or other arrangements that may be necessary or desirable to develop, manufacture or commercialize our product candidates;

•

the pricing and reimbursement of our current product candidates and other product candidates we may develop, if approved;

•

the rate and degree of market acceptance and clinical utility of our current product candidates and other product candidates we may develop;

•

our estimates regarding expenses, future revenue, capital requirements and needs for additional financing;

•

our financial performance;

•

the period over which we estimate our existing cash and cash equivalents will be sufficient to fund our future operating expenses and capital expenditure requirements;

•

the impact of laws and regulations;

•

our expectations regarding the period during which we will remain an emerging growth company under the JOBS Act; and

•

our anticipated use of our existing resources.

Item 1.

Business

1

Identifying unmet need in validated oncogenic drivers. Our relationships with prominent academic centers provide insight into the drug targets that are validated oncogenic drivers, along with innate or acquired resistance and new patient populations that represent the unmet need.

2

Deep Medicinal Chemistry Expertise. Through our internal expertise in structure based small molecule drug discovery and deep understanding of binding modes and biology, we identify compounds that have the potential to achieve a best-in-class product profile spanning alteration coverage including resistance mutations, selectivity, and pharmaceutical properties.

3

Leveraging Tailored Ecosystem of Partners. We leverage an ecosystem of a number of commercial and academic partners  to provide scale to our discovery efforts. For example, we have approximately 70 medicinal chemists at contract research organizations (CROs) working on our pipeline and a number of sponsored research agreements (SRAs) at prominent academic centers to advance the development of our targeted therapies.

•

Rapidly advance the development of our lead targeted therapy RAF and FGFR candidates, KIN-2787 and KIN-3248 respectively. Our lead product candidates are designed to address clinically validated cancer targets in patient populations with limited treatment options. KIN-2787 is designed to address either Class II and Class III BRAF or NRAS alterations. KIN-3248 is designed to address FGFR2 and FGFR3 genomic alterations. We believe that these small molecule candidates offer the potential for substantial clinical benefit when administered as monotherapy. Additionally, because of their enhanced pharmacological properties, we believe there may be future opportunities for combination therapy development. In April 2021, we filed an IND application for KIN-2787 with the FDA. The FDA cleared our IND for KIN-2787 in May 2021 and we initiated a Phase 1 clinical trial, KN-8701, for KIN-2787. We began dosing KIN-2787 in humans in the second half of 2021. KN-8701 is currently in the dose escalation portion of the trial. We anticipate initial data from KN-8701 trial in the third quarter of 2022. KIN-2787 has also demonstrated preclinical proof of concept in NRAS-mutant melanoma models as a single agent and in combination with binimetinib. Based on this preclinical proof of concept, in January 2022, we announced the addition of NRAS-mutant melanoma patients into our ongoing KN-8701 trial both in monotherapy and in combination with binimetinib. We anticipate initiating the combination portion of the trial in the first half of 2022. In January 2022, the FDA cleared our IND for KIN-3248 and we initiated a Phase 1 clinical trial for KIN-3248 in the first quarter of 2022.

•

Develop a pipeline of product candidates focused on overcoming the limitations of current targeted oncology therapeutics. Currently, it is estimated that only 10% of all patients with advanced or metastatic cancer today are eligible for commercially available small molecule kinase inhibitors. Additionally, up to half of these patients may not respond to these treatments and up to half of those who do initially respond may develop resistance. Ultimately, it is estimated that only 2% to 3% of patients with advanced or metastatic cancer will have durable responses to currently available targeted therapeutics. We are therefore focused on developing drugs that can:

o

Target known oncogenic drivers (e.g., Class II or Class III BRAF alterations) in selected cancer types that are not currently addressed by approved therapies. Our BRAF-targeting small molecule kinase inhibitors exemplify this strategy. The successful development and FDA approval of three BRAF-targeted kinase inhibitor drugs for use in Class I BRAF alterations establishes BRAF as a validated cancer drug target.

o

Overcome acquired resistance mutations to existing targeted therapies, potentially improving the durability of response. For example, in our FGFR program we seek to develop targeted therapies that cover initial genomic alterations and preemptively address acquired resistance mutations that arise with current targeted therapies.

o

Treat non-responders to currently approved therapies where advancements in next generation sequencing have identified, and will continue to reveal, genomic drivers of intrinsic resistance. We expect to develop our CDK12 inhibitor and future programs that will target mechanisms of intrinsic resistance.

•

Increase our probability of clinical success by prioritizing known oncogenic drivers for development and incorporating biomarkers into preclinical and clinical development and exploring continual translational research. Typically, drug development carries high attrition rates from the preclinical stage through FDA approval, with some studies showing that only approximately 10% of the candidates entering Phase 1 trials are ultimately approved. We aim to improve the probability of clinical success through several approaches:

o

Targeting known oncogenic drivers. We attempt to select targets for drug development that behave as oncogenic drivers, which increases the likelihood of seeing objective measures of tumor responses early in clinical development. If we are successful in inhibiting these targets with our product candidates, we may increase the likelihood of achieving tumor responses. This approach has been successful for kinase inhibitors designed to treat patients with oncogenic alterations in lung cancer, melanoma, leukemia and other types of cancer.

o

Developing small molecule kinase inhibitors. Small molecule kinase inhibitors are a proven modality that has demonstrated success in the past with multiple currently approved drugs across many solid tumor and hematologic malignancy indications. By testing our molecules against in vitro and in vivo models utilized by prior approved drugs, we believe we can efficiently benchmark and optimize our compounds.

o

Incorporating biomarkers into our preclinical and clinical development. By evaluating a wide range of biomarkers in our preclinical studies and our human clinical trials, we can more rapidly determine patient populations that may or may not respond to our candidates. Continuing to use biomarkers in clinical trials allows us to potentially select defined patient populations that may demonstrate a stronger benefit and thereby ultimately increase our probability of success.

o

Continual translational research. Through extensive translational research starting from preclinical studies through clinical development, we can potentially identify new patient populations, responsive subsets and resistance mechanisms to our candidates. This also provides input into combination strategies we may explore with our candidates. Further, investment in molecular landscape collaborations can also help us refine the unmet need for our candidates and outcomes of existing therapies.

•

Leverage our existing relationships, collaborations and experience to efficiently develop and expand our product portfolio. Our team has extensive experience in identifying, discovering, developing and commercializing innovative cancer therapeutics. We are combining this broad oncology expertise with a network of collaborators to further develop our existing pipeline as well as to identify new research and development opportunities. We have established deep collaborations with leaders, with whom we have advisory agreements, at experienced precision medicine cancer centers and research institutions, including Massachusetts General Hospital Cancer Center and University of California, San Francisco, with whom we have  sponsored research agreements, Memorial Sloan Kettering Cancer Center and Moores Cancer Center at UCSD. These collaborations allow us to explore the mechanistic understanding of the biology of our targets and sensitivity and resistance to our molecules. We have also leveraged our relationships to build a network of global external partners to advance our pipeline. For example, we have service agreements with academic and industrial partners who contribute highly enabling technologies and services that include: (1) approximately 70 medicinal chemists at leading CROs that we can modulate utilization based on needs, (2) bioinformatics support for our translational research efforts, (3) crystallography and biophysical assay platforms to enable structure-based drug discovery, (4) biochemical and cell-based assays to guide lead generation and optimization, and (5) patient-derived organoid and xenograft models to translate our findings to the clinical setting. We utilize these collaborations and partnerships in many aspects of preclinical development for our pipeline of candidates and anticipate further utilizing them in our clinical development efforts. Additionally, these collaborations and partnerships may allow us to accelerate identification of new opportunities, including new patient populations we may target to understand emerging mechanisms of resistance.

1

Identifying unmet need in validated oncogenic drivers. Our relationships with prominent academic centers provide insight into the drug targets that are validated oncogenic drivers, along with innate or acquired resistance and new patient populations that represent the unmet need.

•

those with cancers that harbor known oncogenic drivers with no currently available targeted therapies;

•

those with genomically well-characterized tumors that have intrinsic resistance to currently available treatments (non-responders); and

•

those whose tumors have acquired resistance over the course of therapy to currently available treatments.

•

define emerging patient populations;

•

demonstrate selective in vitro and in vivo activity and define dose-exposure pharmacodynamic (PD) relationships in clinically relevant models;

•

test prioritized compounds against specific mutations and fusions;

•

investigate mechanism of action-the specific biochemical interaction through which a drug substance produces its pharmacological effect-to support the refinement of strategies for patient selection and patient stratification for both monotherapy and rationale combinations; and

•

develop biomarker-based development strategies that will drive patient selection in our clinical programs.

•

Class I: BRAF alterations where BRAF monomers activate the MAPK signaling pathway.

•

Class II: BRAF alterations that generate BRAF homodimers, where two BRAF molecules combine, which are RAS-independent and activate the MAPK pathway. These are frequently the result of point mutations, indels or gene fusions, in which the kinase domain of BRAF is aberrantly joined to a partner gene.

•

Class III: BRAF alterations with minimal kinase activity that induce BRAF’s dimerization to other RAF kinase family members (e.g., ARAF or CRAF), creating a RAF heterodimer with enhanced affinity to activated RAS and increased enzymatic activity and downstream signaling.

	BRAF Class II and Class III Alterations			NRAS mutant
	Advanced and Metastatic NSCLC	Advanced and Metastatic Melanoma	Other Advanced and Metastatic Solid Tumors+	Advanced and Metastatic Melanoma
Biomarker Prevalence	3%	9%	1-3%	~25%

•

inhibit RAF across both sides of the RAF dimer, which enables populations beyond Class I alterations to be targeted;

•

enable large drug exposures in vivo for BRAF mutant target coverage while avoiding pathway rebound; and

•

target Class II and Class III BRAF alterations, which has been enabled by technological advances and increased access to genomic profiling.

•

Part A1: Dose Escalation (Monotherapy): Patients with advanced or metastatic solid tumors bearing any BRAF Class I, Class II or Class III alteration (including NSCLC, melanoma and other solid tumors) or NRAS-mutant melanoma will be enrolled in cohorts of 1 to 3 patients (modified 3+3 design) each to receive oral KIN-2787 monotherapy for up to 40 patients.

•

Part A2: Dose Escalation (Combination with Binimetinib): Patients, including those with advanced or metastatic NRAS-mutant melanoma will be enrolled in cohorts of 3 patients (3+3 design) each to receive oral KIN-2787 in combination with binimetinib for up to approximately 36 patients.

•

Part B: Dose Expansion: Patients with advanced or metastatic solid tumors bearing either a Class II or Class III BRAF alteration (including NSCLC, melanoma and other solid tumors, but excluding Class I alteration-driven cancers) will be enrolled in one of a number of cohorts defined by cancer type or BRAF alteration of up to 20 to 30 patients per cohort to receive oral KIN-2787 as a single anti-cancer agent.

•

Part A: Dose Escalation: Patients with advanced or metastatic solid tumors in both FGFR inhibitor naïve and pre-treated patient populations with molecularly-defined FGFR2- and/or FGFR3-alteration driven cancers, including a limited number of patients with FGFR2 or FGFR3 amplification-driven cancers. Patients will be enrolled in cohorts of 3 patients each to receive oral KIN-3248 as a single agent for up to 45 patients.

•

Part B: Dose Expansion: Patients with advanced or metastatic solid tumors bearing with molecularly-defined FGFR2- and/or FGFR3-alteration driven cancers will be enrolled in one of a number of cohorts defined by disease or biomarker of up to 20 to 30 patients per cohort to receive oral KIN-3248 as a single agent. This would include both FGFR inhibitor naïve and pre-treated patient populations.

•

significantly augment the clinical benefits of PARP inhibitors, chemotherapeutic agents and ICIs in the subset of these cancer patients who are currently eligible to be treated with these drugs; and

•

therapeutically sensitize cancers from expanded populations of OC, mCRPC and TNBC patients who are not currently eligible to receive PARP inhibitors or ICIs, and who yet may gain substantial benefit from combination therapy with either PARP inhibitors, conventional chemotherapies, or an ICI agent.

•

define emerging patient populations;

•

demonstrate selective in vitro and in vivo activity and define dose-exposure pharmacodynamic relationships in clinically relevant models;

•

test prioritized compounds against specific mutations and fusions;

•

investigate mechanism of action-the specific biochemical interaction through which a drug substance produces its pharmacological effect-to support the refinement of strategies for patient selection and patient stratification for both monotherapy and rationale combinations; and

•

develop biomarker-based development strategies that will drive patient selection in our clinical programs.

•

completion of extensive preclinical studies in accordance with applicable regulations, including studies conducted in accordance with GLP;

•

submission to the FDA of an IND, which must become effective before human clinical trials may begin;

•

approval by an independent IRB, or ethics committee at each clinical trial site before each trial may be initiated;

•

performance of adequate and well-controlled human clinical trials in accordance with applicable IND regulations, good clinical practice (GCP) requirements and other clinical trial-related regulations to establish substantial evidence of the safety and efficacy of the investigational product for each proposed indication;

•

submission to the FDA of an NDA after completion of all pivotal trials;

•

determination by the FDA within 60 days of its receipt of an NDA to accept the filing for substantive review;

•

satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug will be produced to assess compliance with cGMP requirements assuring that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

•

potential FDA audit of the preclinical study and/or clinical trial sites that generated the data in support of the NDA filing;

•

FDA review and approval of the NDA, including consideration of the views of any FDA advisory committee, prior to any commercial marketing or sale of the drug in the United States; and

•

compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy (REMS), and the potential requirement to conduct post-approval studies.

•

Phase 1 clinical trials generally involve a small number of healthy volunteers or disease-affected patients who are initially exposed to a single dose and then multiple doses of the product candidate. The primary purpose of these clinical trials is to assess the metabolism, pharmacologic action, tolerability and safety of the drug.

•

Phase 2 clinical trials involve studies in disease-affected patients to determine the dose and dosing schedule required to produce the desired benefits. At the same time, safety and further pharmacokinetic and pharmacodynamic information is collected, possible adverse effects and safety risks are identified, and a preliminary evaluation of efficacy is conducted.

•

Phase 3 clinical trials generally involve a large number of patients at multiple sites and are designed to provide the data necessary to demonstrate the effectiveness of the product for its intended use and its safety in use, and to establish the overall benefit/risk relationship of the product and provide an adequate basis for product approval. These trials may include comparisons with placebo and/or other comparator treatments. The duration of treatment is often extended to mimic the actual use of a product during marketing.

•

restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market, or product recalls;

•

fines, warning letters, or holds on post-approval clinical studies;

•

refusal of the FDA to approve pending applications or supplements to approved applications;

•

suspension or revocation of product approvals;

•

product seizure or detention;

•

refusal to permit the import or export of products; and

•

injunctions or the imposition of civil or criminal penalties.

•

The federal Anti-Kickback Statute, which makes it illegal for any person, including a prescription drug manufacturer (or a party acting on its behalf), to knowingly and willfully solicit, receive, offer or pay any remuneration that is intended to induce or reward referrals, including the purchase, recommendation, order or prescription of a particular drug, for which payment may be made under a federal healthcare program, such as Medicare or Medicaid. Moreover, the ACA provides that the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act.

•

The federal false claims, including the civil False Claims Act that can be enforced by private citizens through civil whistleblower or qui tam actions, and civil monetary penalties prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government, and/or impose exclusions from federal health care programs and/or penalties for parties who engage in such prohibited conduct.

•

The Federal Health Insurance Portability and Accountability Act of 1996 (HIPAA), prohibits, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters.

•

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their implementing regulations also impose obligations on covered entities such as health insurance plans, healthcare clearinghouses, and certain health care providers and their respective business associates, including mandatory contractual terms as well as their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.

•

Analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, state laws that require biotechnology companies to comply with the biotechnology industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state and local laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures and require the registration of their sales representatives, state laws that require biotechnology companies to report information on the pricing of certain drug products, and state and foreign laws that govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

•

The Community MA is issued by the European Commission through the Centralized Procedure, based on the opinion of the Committee for Medicinal Products for Human Use (CHMP), of the EMA, and is valid throughout the entire territory of the EEA. The Centralized Procedure is mandatory for certain types of products, such as biotechnology medicinal products, orphan medicinal products, advanced-therapy medicines such as gene-therapy, somatic cell-therapy or tissue-engineered medicines and medicinal products containing a new active substance indicated for the treatment of HIV, AIDS, cancer, neurodegenerative disorders, diabetes, auto-immune and other immune dysfunctions and viral diseases. The Centralized Procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU.

•

National MAs, which are issued by the competent authorities of the Member States of the EEA and only cover their respective territory, are available for products not falling within the mandatory scope of the Centralized Procedure. Where a product has already been authorized for marketing in a Member State of the EEA, this National MA can be recognized in another Member States through the Mutual Recognition Procedure. If the product has not received a National MA in any Member State at the time of application, it can be approved simultaneously in various Member States through the Decentralized Procedure. Under the Decentralized Procedure an identical dossier is submitted to the competent authorities of each of the Member States in which the MA is sought, one of which is selected by the applicant as the Reference Member State (RMS). The competent authority of the RMS prepares a draft assessment report, a draft summary of the product characteristics (SOPC), and a draft of the labeling and package leaflet, which are sent to the other Member States (referred to as the Member States Concerned) for their approval. If the Member States Concerned raise no objections, based on a potential serious risk to public health, to the assessment, SOPC, labeling or packaging proposed by the RMS, the product is subsequently granted a national MA in all the Member States (i.e., in the RMS and the Member States Concerned).

•

Our mission is to expand the reach of targeted therapeutics by developing products that are designed to address significant unmet need for those battling cancer. Our two lead product candidates, KIN-2787 and KIN-3248, could impact over 100,000 prevalent patients and their caregivers. For example, for KIN-2787, patients with Class II or Class III alterations have no available targeted therapy treatment options today and for KIN-3248, patients who have been treated first-generation FGFR inhibitors often develop resistance to treatment, which shortens their duration of response.  We estimate that each month of life extension for patients could lead to a risk adjusted lifetime value of over $1 billion for both programs. Further, caregivers of cancer patients are typically forced to significantly change their lives in order to provide care, which can lead to increased psychological morbidity and economic burden. Approximately 50% of caregivers experience severe decline of quality of life. Providing new treatment options for patients who are currently underserved could improve caregivers’ quality of life.

•

We are committed to being an equal opportunity employer and enhancing diversity and inclusion across our business. Our Code of Business Conduct and Ethics prohibits discrimination of any protected group and our managers and other employees participate in anti-harassment training.

•

We strive to and are always improving our diversity and inclusion (D&I) strategies and performance, and we are proud of the gender and ethnic diversity we have cultivated throughout the company. As of December 31, 2021, of our 61 full-time employees, 27 are female and 29 are ethnically diverse. We intend to continue to develop our D&I practices and improve performance across our workforce.

•

We are an employee-focused company dedicated to building a talented and motivated team and as such offer competitive compensation and comprehensive benefits to attract and retain top talent. In addition to offering benefits such as medical, dental, vision, 401(k) with company contribution, flexible spending for healthcare and dependent care, life insurance, pet insurance, voluntary life-illness-accident insurance, and both short and long-term disability, we offer work / life balance benefits and employee development opportunities. These include unlimited paid time off (vacation, sick leave), annual paid “refresher” days, annual massage days, healthy lifestyle reimbursement programs, home office reimbursement programs and flexible office and remote work options. We also have a variety of company-wide events to support and encourage relationship development, teamwork and collaboration (which we view as essential to our success as a result of the COVID-19 pandemic).

•

In 2021, we commenced the first offering period under the Kinnate Biopharma Inc. 2020 Employee Stock Purchase Plan for all full-time employees. This is a benefit we are delighted to offer and that we believe will help to further incentivize our employees to contribute to our achievement of business success.

•

In an effort to ensure the safety of our staff and clinical patients during the COVID-19 pandemic and during subsequent surges, we have limited in person attendance in our offices and adopted state mandated protocols. We have also enforced a vaccine mandate for all employees and others visiting our offices (subject to applicable law).

•

We are subject to numerous environmental, health and safety laws and regulations.

•

Our employees are required to promptly report any known or suspected violations of environmental laws or any events that may result in a discharge or emission of hazardous materials.

•

We have recycling in all facilities.

•

We minimize use of disposable bottles and printing of paper.

•

Our new facility in San Diego is LEED certified.

•

We have commuter benefits programs in place that encourage employees to walk, bike or utilize public transportation instead of cars for their commute.

•

We encourage video conferencing for non-essential meetings to reduce travel and commute emissions.

•

We have a diverse board of directors that currently includes three female members. In addition, two of our directors, including one of our female directors, are of Middle Eastern (Persian) descent. We believe that these four directors provide valuable diversity to our board’s membership.

•

Our board of directors and executive management team have oversight of all the ESG commitments that we have outlined in this section.

•

We have adopted policies and procedures and conduct training to ensure appropriate management of data privacy and cybersecurity risks. We also have an information security incident response plan that defines our process for investigating, reporting and managing cybersecurity incidents and/or data breaches.  Our cybersecurity and privacy programs are overseen by our Chief Operating Officer and General Counsel.

•

We have adopted a Code of Business Conduct and Ethics with provisions related to corporate ethics, bribery and corruption, whistleblower policies, political involvement and other dimensions of corporate ethics.

Item 1A.

Risk Factors

•

We are early in our development efforts and have a limited operating history and no products approved for commercial sale.

•

We have incurred significant net losses and expect to continue to incur significant net losses for the foreseeable future.

•

Our ability to generate revenue and achieve profitability depends on our ability to achieve our objectives relating to discovery, development and commercialization of our product candidates.

•

We will require substantial additional capital to finance our operations.

•

We are substantially dependent on our RAF and FGFR programs.

•

Our preclinical studies and clinical trials may fail to demonstrate the safety and efficacy of our product candidates.

•

Our discovery and development activities are focused on the development of therapeutics in an evolving area of science.

•

The outcome of testing and early clinical trials may not be predictive of the success of later clinical trials.

•

In addition to our RAF and FGFR programs, our prospects depend in part upon discovering, developing and commercializing product candidates from our CDK12 and other research programs.

•

Our approach to the discovery and development of product candidates is unproven.

•

The regulatory approval processes of regulatory authorities are lengthy, time consuming and unpredictable.

•

We have limited experience as a company in conducting clinical trials.

•

We may not be able to file INDs on the timelines we expect.

•

Our product candidates may cause significant adverse events, toxicities or other undesirable side effects.

•

Data from our preclinical studies and clinical trials may change as more data become available and are subject to verification.

•

We could experience delays or difficulties in the enrollment or maintenance of patients in clinical trials.

•

The COVID-19 pandemic could adversely impact our business.

•

We face substantial competition which may result in others discovering, developing or commercializing products before us.

•

The manufacture of drugs is complex, and third-party manufacturers may encounter production difficulties.

•

Our product candidates may not achieve adequate market acceptance among the medical community.

•

The market opportunities for our product candidates may be limited to certain smaller patient subsets.

•

Our product candidates may become subject to unfavorable third-party coverage and reimbursement practices.

•

Our business entails a significant risk of product liability.

•

We may be unable to obtain regulatory approval and be unable to commercialize our product candidates.

•

We may develop our product candidates with other therapies, which would expose us to additional risks.

•

We have never commercialized a product candidate as a company and currently lack the resources to do so on our own or with others.

•

Regulatory authorities may not accept data from clinical trials conducted in locations outside of their jurisdiction.

•

Obtaining regulatory approval in one jurisdiction does not mean we will be successful in other jurisdictions.

•

Any product candidates that receive regulatory approval will be subject to post-marketing regulations.

•

Regulatory authorities actively enforce the laws and regulations prohibiting the promotion of off-label uses.

•

Failure to obtain approval of a required companion diagnostic test, will prevent commercialization of the product candidate.

•

Where appropriate, we plan to secure approval from regulatory authorities through accelerated registration pathways. If we are unsuccessful, we may be required to conduct additional preclinical studies or clinical trials.

•

We may seek, but not obtain, Fast Track designation from the FDA for one or more of our product candidates.

•

A Breakthrough Therapy designation by the FDA may not lead to a faster review or approval process.

•

We may not be able to obtain orphan drug designation or orphan drug exclusivity for one or more of our product candidates.

•

We may face difficulties from changes to current regulations and future legislation.

•

Our relationships with healthcare professionals, clinical investigators, CROs and third-party payors may be subject to reporting requirements and various laws.

•

We must comply with regulations governing the use, processing and cross-border transfer of personal information.

•

Our employees, service providers, suppliers and vendors may engage in misconduct or other improper activities.

•

Our business activities may be subject to the U.S. Foreign Corrupt Practices Act (FCPA) and similar foreign laws, as well as U.S. and foreign export controls, trade sanctions, and import laws and regulations.

•

If we fail to comply with California laws or Nasdaq rules governing the diversity of our board of directors, we could be exposed to financial penalties and suffer reputational harm.

•

Our success is highly dependent on our ability to attract, hire and retain highly skilled executive officers and employees.

•

We will need to grow the size and capabilities of our organization, and we may experience difficulties in managing growth.

•

Our internal computer systems, or those of any of our service providers, may fail or suffer security or data privacy breaches or incidents.

•

Many of our research and preclinical activities are conducted by third parties outside of the United States, including in China.

•

Our operations are vulnerable to interruption by natural disasters, war, terrorist activity, pandemics and other events.

•

If we are unable to establish sales or marketing capabilities or enter into agreements with third parties to sell or market our product candidates, we may not be able to successfully sell or market our product candidates that obtain regulatory approval.

•

A variety of risks associated with marketing our product candidates internationally could adversely affect our business.

•

Our ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited.

•

Our success depends on our ability to protect our intellectual property and our proprietary technologies.

•

The scope of our patent protection may not be sufficiently broad, or we could lose patent protection.

•

Intellectual property rights do not necessarily address all potential threats to our competitive advantage.

•

Our commercial success depends on our operating without infringing the patents and other proprietary rights of third parties.

•

We may not be successful in obtaining or maintaining rights to our future product candidates.

•

We may be involved in lawsuits to protect or enforce our patents or our future licensors’ patents.

•

The outcome of derivation proceedings may require us to cease using or attempt to license the related technology.

•

Patent reform legislation may increase uncertainties and costs of prosecuting patent applications and enforcing issued patents.

•

Changes in patent law could diminish the value of patents in general.

•

We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.

•

Patent terms may be inadequate to protect our competitive position on our product candidates.

•

If we do not obtain patent term extension for our product candidates, our business may be materially harmed.

•

We may not be able to protect our intellectual property rights throughout the world.

•

We rely on third parties to conduct our preclinical studies and clinical trials, and they may not perform satisfactorily.

•

We contract with third parties for the manufacture of our product candidates for preclinical studies and clinical trials and expect to continue to do so for additional preclinical studies, clinical trials and ultimately for commercialization.

•

Our manufacturing process needs to comply with FDA regulations relating to the quality and reliability of such processes.

•

If we engage in future acquisitions or strategic partnerships, this may increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks.

•

If our manufacturers use hazardous materials in a manner that causes injury or violates law, we may be liable for damages.

•

If we decide to establish collaborations, we may have to alter our development and commercialization plans.

•

The market price of our common stock is volatile, which could result in substantial losses for investors.

•

If securities analysts do not publish research or reports about our business, or if they publish adverse reports regarding us, our stock price and trading volume could decline.

•

If our remediation of a material weakness that we identified in our internal control over financial reporting is not effective, we may not be able to accurately or timely report our financial condition or results of operations.

•

Delaware law and provisions in our charter documents might prevent a change in control of our company or changes in our management, depressing the market price of our common stock.

•

Our charter documents provide exclusive forums for disputes between us and our stockholders, limiting their ability to obtain a favorable judicial forum.

•

successful and timely completion of clinical development of product candidates from our RAF program and preclinical and clinical development of product candidates from our FGF program, our CDK12 and other research programs, and any other future programs;

•

establishing and maintaining relationships with CROs and clinical sites for the clinical development of product candidates from our RAF and FGFR programs, our CDK12 and other research programs, and any other future programs;

•

timely receipt of marketing approvals from applicable regulatory authorities for any product candidates for which we successfully complete clinical development;

•

developing an efficient and scalable manufacturing process for our product candidates, including obtaining finished products that are appropriately packaged for sale;

•

establishing and maintaining commercially viable supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and meet the market demand for our product candidates, if approved;

•

successful commercial launch following any marketing approval, including the development of a commercial infrastructure, whether in-house or with one or more collaborators;

•

a continued acceptable safety profile following any marketing approval of our product candidates;

•

commercial acceptance of our product candidates by patients, the medical community and third-party payors;

•

satisfying any required post-marketing approval commitments to applicable regulatory authorities;

•

identifying, assessing and developing new product candidates;

•

obtaining, maintaining and expanding patent protection, trade secret protection and regulatory exclusivity, both in the United States and internationally;

•

defending against third-party interference or infringement claims, if any;

•

entering into, on favorable terms, any collaboration, licensing or other arrangements that may be necessary or desirable to develop, manufacture or commercialize our product candidates;

•

obtaining coverage and adequate reimbursement by third-party payors for our product candidates;

•

addressing any competing therapies and technological and market developments; and

•

attracting, hiring and retaining qualified personnel.

•

successful and timely completion of preclinical studies;

•

approval of INDs for our planned clinical trials and future clinical trials;

•

addressing any potential delays resulting from factors related to the COVID‑19 pandemic;

•

successful initiation and completion of clinical trials;

•

successful and timely patient selection and enrollment in and completion of clinical trials;

•

maintaining and establishing relationships with CROs and clinical sites for the clinical development of our product candidates both in the United States and internationally;

•

the frequency and severity of adverse events in clinical trials;

•

demonstrating efficacy, safety and tolerability profiles that are satisfactory to the FDA, EMA or any comparable foreign regulatory authority for marketing approval;

•

the timely receipt of marketing approvals from applicable regulatory authorities;

•

the timely identification, development and approval of companion diagnostic tests, if required;

•

the extent of any required post-marketing approval commitments to applicable regulatory authorities;

•

the maintenance of existing or the establishment of new supply arrangements with third-party drug product suppliers and manufacturers for clinical development and, if approved, commercialization of our product candidates;

•

obtaining and maintaining patent protection, trade secret protection and regulatory exclusivity, both in the United States and internationally;

•

the protection of our rights in our intellectual property portfolio;

•

the successful launch of commercial sales following any marketing approval;

•

a continued acceptable safety profile following any marketing approval;

•

commercial acceptance by patients, the medical community and third-party payors; and

•

our ability to compete with other therapies.

•

failure of our product candidates in preclinical studies or clinical trials to demonstrate safety and efficacy;

•

receipt of feedback from regulatory authorities that requires us to modify the design of our clinical trials;

•

negative or inconclusive clinical trial results that may require us to conduct additional clinical trials or abandon certain research and/or drug development programs;

•

the number of patients required for clinical trials being larger than anticipated, enrollment in these clinical trials being slower than anticipated or participants dropping out of these clinical trials at a higher rate than anticipated;

•

third-party contractors failing to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;

•

the suspension or termination of our clinical trials for various reasons, including non-compliance with regulatory requirements or a finding that our product candidates have undesirable side effects or other unexpected characteristics or risks;

•

the cost of clinical trials of our product candidates being greater than anticipated;

•

the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates being insufficient or inadequate; and

•

regulators revising the requirements for approving our product candidates.

•

generating sufficient data to support the initiation or continuation of preclinical studies and clinical trials;

•

addressing any delays resulting from factors related to the COVID‑19 pandemic;

•

obtaining regulatory permission to initiate clinical trials;

•

contracting with the necessary parties to conduct clinical trials;

•

successful enrollment of patients in, and the completion of, clinical trials on a timely basis;

•

the timely manufacture of sufficient quantities of a product candidate for use in clinical trials; and

•

adverse events in clinical trials.

•

the FDA, EMA or other comparable foreign regulatory authorities may disagree with the design, implementation or results of our clinical trials;

•

the FDA, EMA or other comparable foreign regulatory authorities may determine that we have not demonstrated the safety and efficacy of our product candidates, or that they undesirable or unintended side effects, toxicities or other characteristics that preclude our obtaining marketing approval or prevent or limit commercial use;

•

the population studied in the clinical trial may not be sufficiently broad or representative to assure efficacy and safety in the full population for which we seek approval;

•

the FDA, EMA or other comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;

•

we may be unable to demonstrate to the FDA, EMA or other comparable foreign regulatory authorities that a product candidate’s risk-benefit ratio for its proposed indication is acceptable;

•

the FDA, EMA or other comparable foreign regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications or facilities of third-party manufacturers with which we contract for clinical and commercial supplies;

•

the FDA, EMA or other comparable regulatory authorities may fail to approve companion diagnostic tests required for our product candidates; and

•

the approval policies or regulations of the FDA, EMA or other comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.

•

size and nature of the patient population;

•

severity of the disease under investigation;

•

availability and efficacy of approved drugs for the disease under investigation;

•

patient eligibility criteria for the clinical trial in question as defined in the protocol, including biomarker-driven identification and/or certain highly-specific criteria related to stage of disease progression, which may limit the patient populations eligible for our clinical trials to a greater extent than competing clinical trials for the same indication that do not have biomarker-driven patient eligibility criteria;

•

perceived risks and benefits of the product candidate under study;

•

clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved or other product candidates being investigated for the indications we are investigating;

•

clinicians’ willingness to screen their patients for biomarkers to indicate which patients may be eligible for enrollment in our clinical trials;

•

patient referral practices of physicians;

•

the ability to monitor patients adequately during and after treatment;

•

proximity and availability of clinical trial sites for prospective patients; and

•

the risk that patients enrolled in clinical trials will drop out of the clinical trials before completion or, because they may be late-stage cancer patients, will not survive the full terms of the clinical trials.

•

delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff;

•

delays or difficulties in enrolling and retaining patients in any clinical trials, particularly elderly subjects, who are at a higher risk of severe illness or death from COVID‑19;

•

difficulties interpreting data from our clinical trials due to the possible effects of COVID‑19 on patients;

•

diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of clinical trials;

•

interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal or state governments, employers and others;

•

interruption or delays in the operations of the FDA, EMA or other regulatory authorities, which may impact review and approval timelines;

•

limitations in resources that would otherwise be focused on the conduct of our business, our preclinical studies or our clinical trials, including because of sickness or the desire to avoid contact with large groups of people or as a result of government-imposed “shelter in place” or similar working restrictions;

•

interruptions, difficulties or delays arising in our existing operations and company culture as a result of our employees including those hired during the COVID‑19 pandemic, working from home or in a hybrid model;

•

delays in receiving approval from regulatory authorities to initiate our clinical trials;

•

delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials; interruptions in preclinical studies due to restricted or limited operations at the CROs conducting such studies;

•

interruption in global freight and shipping that may affect the transport of clinical trial materials, such as investigational drug product to be used in our clinical trials;

•

changes in regulations as part of a response to the COVID‑19 pandemic which may require us to change the ways in which our clinical trials are to be conducted, or to discontinue the clinical trials altogether, or which may result in unexpected costs;

•

delays in necessary interactions with regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government or contractor personnel; and

•

refusal of the FDA, EMA or other regulatory authorities to accept data from clinical trials in affected geographies outside of their respective jurisdictions.

•

the efficacy and safety profile as demonstrated in clinical trials compared to alternative treatments;

•

the timing of market introduction of the product candidate as well as competitive products;

•

the clinical indications for which a product candidate is approved;

•

restrictions on the use of product candidates in the labeling approved by regulatory authorities, such as boxed warnings or contraindications in labeling, or a risk evaluation and mitigation strategy, if any, which may not be required of alternative treatments and competitor products;

•

the potential and perceived advantages of our product candidates over alternative treatments;

•

the cost of treatment in relation to alternative treatments;

•

the availability of coverage and adequate reimbursement by third-party payors, including government authorities;

•

the availability of an approved product candidate for use as a combination therapy;

•

relative convenience and ease of administration;

•

the willingness of the target patient population to try new therapies and undergo required diagnostic screening to determine treatment eligibility and of physicians to prescribe these therapies and diagnostic tests;

•

the effectiveness of sales and marketing efforts;

•

unfavorable publicity relating to our product candidates; and

•

the approval of other new therapies for the same indications.

•

the FDA, EMA or other comparable foreign regulatory authorities may disagree with the design, implementation or results of our clinical trials;

•

the FDA, EMA or other comparable foreign regulatory authorities may determine that we have not demonstrated the safety and efficacy of our product candidates, or that they have undesirable or unintended side effects, toxicities or other characteristics that preclude our obtaining marketing approval or prevent or limit commercial use;

•

the population studied in the clinical trial may not be sufficiently broad or representative to assure efficacy and safety in the full population for which we seek approval;

•

the FDA, EMA or other comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;

•

we may be unable to demonstrate to the FDA, EMA or other comparable foreign regulatory authorities that our product candidate’s risk-benefit ratio for its proposed indication is acceptable;

•

the FDA, EMA or other comparable foreign regulatory authorities may fail to approve the manufacturing processes, test procedures and specifications or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and

•

the approval policies or regulations of the FDA, EMA or other comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.

•

delays in or the rejection of product approvals;

•

restrictions on our ability to conduct clinical trials, including full or partial clinical holds on ongoing or planned clinical trials;

•

restrictions on the products, manufacturers or manufacturing process;

•

warning or untitled letters;

•

civil and criminal penalties;

•

injunctions;

•

suspension or withdrawal of regulatory approvals;

•

product seizures, detentions or import bans;

•

voluntary or mandatory product recalls and publicity requirements;

•

total or partial suspension of production;

•

imposition of restrictions on operations, including costly new manufacturing requirements;

•

revisions to the labeling, including limitation on approved uses or the addition of additional warnings, contraindications or other safety information, including boxed warnings;

•

imposition of a REMS, which may include distribution or use restrictions; and

•

requirements to conduct additional post-market clinical trials to assess the safety of products.

•

the demand for our product candidates, if we obtain regulatory approval;

•

our ability to set a price that we believe is fair for our products;

•

our ability to obtain coverage and reimbursement approval for a product;

•

our ability to generate revenue and achieve or maintain profitability;

•

the level of taxes that we are required to pay; and

•

the availability of capital.

•

the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, either the referral of an individual, or the purchase, lease, order or recommendation of any good, facility, item or service for which payment may be made, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. Violations are subject to civil and criminal fines and penalties for each violation, plus up to three times the remuneration involved, imprisonment, and exclusion from government healthcare programs. In addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act (FCA). There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, but the exceptions and safe harbors are drawn narrowly and require strict compliance in order to offer protection;

•

federal civil and criminal false claims laws, including the FCA, which can be enforced through civil “qui tam” or “whistleblower” actions, and civil monetary penalty laws, impose criminal and civil penalties against individuals or entities for, among other things, knowingly presenting, or causing to be presented, claims for payment or approval from Medicare, Medicaid, or other federal health care programs that are false or fraudulent; knowingly making or causing a false statement material to a false or fraudulent claim or an obligation to pay money to the federal government; or knowingly concealing or knowingly and improperly avoiding or decreasing such an obligation. Manufacturers can be held liable under the FCA even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. The FCA also permits a private individual acting as a “whistleblower” to bring actions on behalf of the federal government alleging violations of the FCA and to share in any monetary recovery. When an entity is determined to have violated the federal civil FCA, the government may impose civil fines and penalties for each false claim, plus treble damages, and exclude the entity from participation in Medicare, Medicaid and other federal healthcare programs;

•

HIPAA, which created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person or entity can be found guilty of violating HIPAA without actual knowledge of the statute or specific intent to violate it;

•

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (HITECH), and their respective implementing regulations, which impose requirements on certain covered healthcare providers, health plans, and healthcare clearinghouses and their respective business associates that perform services for them that involve the use, or disclosure of, individually identifiable health information as well as their covered subcontractors, relating to the privacy, security and transmission of individually identifiable health information without appropriate authorization. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions;

•

the federal Physician Payments Sunshine Act, created under the ACA and its implementing regulations, which require applicable manufacturers of covered drugs, devices, biologicals or medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to HHS information related to payments or other transfers of value made in the previous year to covered recipients, including physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician healthcare professionals (such as physician assistants and nurse practitioners, among others) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; and

•

analogous state and foreign laws and regulations, such as state and foreign anti-kickback, false claims, consumer protection and unfair competition laws which may apply to pharmaceutical business practices, including but not limited to, research, distribution, sales and marketing arrangements as well as submitting claims involving healthcare items or services reimbursed by any third-party payor, including commercial insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government that otherwise restricts payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to file reports with states regarding pricing and marketing information, such as the tracking and reporting of gifts, compensations and other remuneration and items of value provided to healthcare professionals and entities; state and local laws requiring the registration of pharmaceutical sales representatives; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

•

identifying, recruiting, integrating, maintaining, retaining and motivating our current and additional employees;

•

managing our internal development efforts effectively, including the preclinical, clinical, FDA, EMA and other comparable foreign regulatory authorities’ review process for our RAF and FGFR programs and our other product candidates, while complying with any contractual obligations to contractors and other third parties;

•

managing increasing operational and managerial complexity; and

•

improving our operational, financial and management controls, reporting systems and procedures.

---

•

differing regulatory requirements and reimbursement regimes in foreign countries, such as the lack of pathways for accelerated drug approval, may result in foreign regulatory approvals taking longer and being more costly than obtaining approval in the United States;

•

foreign regulatory authorities may disagree with the design, implementation or results of our clinical trials or our interpretation of data from preclinical studies or clinical trials;

•

approval policies or regulations of foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval;

•

impact of the COVID‑19 pandemic on our ability to produce our product candidates and conduct clinical trials in foreign countries;

•

unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements;

•

economic weakness, including inflation, or political instability in particular foreign economies and markets;

•

compliance with legal requirements applicable to privacy, data protection, information security and other matters;

•

compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

•

foreign taxes, including withholding of payroll taxes;

•

foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country;

•

difficulties staffing and managing foreign operations;

•

complexities associated with managing multiple payor reimbursement regimes and government payors in foreign countries;

•

workforce uncertainty in countries where labor unrest is more common than in the United States;

•

potential liability under the FCPA or comparable foreign regulations;

•

challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States;

•

production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad (such as the ongoing conflict between Ukraine and Russia, including the sanctions imposed by the United States, the European Union and others on Russia and other related parties); and

•

business interruptions resulting from geo-political actions, including war and terrorism, trade policies, treaties and tariffs.

•

the USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment and other provisions during the patent process, the noncompliance with which can result in abandonment or lapse of a patent or patent application, and partial or complete loss of patent rights in the relevant jurisdiction;

•

patent applications may not result in any patents being issued;

•

patents may be challenged, invalidated, modified, revoked, circumvented, found to be unenforceable or otherwise may not provide any competitive advantage;

•

our competitors, many of whom have substantially greater resources than we do and many of whom have made significant investments in competing technologies, may seek or may have already obtained patents that will limit, interfere with or eliminate our ability to make, use and sell our potential product candidates;

•

there may be significant pressure on the U.S. government and international governmental bodies to limit the scope of patent protection both inside and outside the United States for disease treatments that prove successful, as a matter of public policy regarding worldwide health concerns; and

•

others may be able to develop products that are similar to our product candidates but that are not covered by the claims of the patents that we own or license;

•

we or our future licensors or collaborators might not have been the first to make the inventions covered by the issued patents or patent application that we own or license;

•

we or our future licensors or collaborators might not have been the first to file patent applications covering certain of our inventions;

•

others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights;

•

it is possible that the pending patent applications we own or license will not lead to issued patents;

•

issued patents that we own or license may be held invalid or unenforceable, as a result of legal challenges by our competitors;

•

our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets;

•

we may not develop additional proprietary technologies that are patentable;

•

the patents of others may have an adverse effect on our business; and

•

we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.

•

result in costly litigation that may cause negative publicity;

•

divert the time and attention of our technical personnel and management;

•

cause development delays;

•

prevent us from commercializing any of our product candidates until the asserted patent expires or is held finally invalid or not infringed in a court of law;

•

require us to develop non-infringing technology, which may not be possible on a cost-effective basis;

•

subject us to significant liability to third parties; or

•

require us to enter into royalty or licensing agreements, which may not be available on commercially reasonable terms, or at all, or which might be non-exclusive, which could result in our competitors gaining access to the same technology.

•

the scope of rights granted under the license agreement and other interpretation-related issues;

•

whether and the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement;

•

our right to sublicense patents and other rights to third parties;

•

our diligence obligations under the license agreement and what activities satisfy those diligence obligations;

•

our right to transfer or assign the license;

•

the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our future licensors and us and our partners; and

•

the priority of invention of patented technology.

•

the failure of the third party to manufacture our product candidates according to our schedule and specifications, or at all, including if our third-party contractors give greater priority to the supply of other products over our product candidates or otherwise do not satisfactorily perform according to the terms of the agreements between us and them;

•

the reduction or termination of production or deliveries by suppliers, or the raising or prices or renegotiation of terms;

•

the termination or nonrenewal of arrangements or agreements by our third-party contractors at a time that is costly or inconvenient for us;

•

the breach by the third-party contractors of our agreements with them;

•

the failure of third-party contractors to comply with applicable regulatory requirements, including cGMPs;

•

the breach by the third-party contractors of our agreements with them;

•

the failure of the third party to manufacture our product candidates according to our specifications;

•

the mislabeling of clinical supplies, potentially resulting in the wrong dose amounts being supplied or active drug or placebo not being properly identified;

•

clinical supplies not being delivered to clinical sites on time, leading to clinical trial interruptions, or of drug supplies not being distributed to commercial vendors in a timely manner, resulting in lost sales; and

•

the misappropriation of our proprietary information, including our trade secrets and know-how.

•

increased operating expenses and cash requirements;

•

the assumption of additional indebtedness or contingent liabilities;

•

the issuance of our equity securities;

•

assimilation of operations, intellectual property, products and product candidates of an acquired company, including difficulties associated with integrating new personnel;

•

the diversion of our management’s attention from our existing programs and initiatives in pursuing such a strategic merger or acquisition;

•

retention of key employees, the loss of key personnel and uncertainties in our ability to maintain key business relationships;

•

risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products, product candidates and marketing approvals; and

•

our inability to generate revenue from acquired technology and/or products sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs.

•

collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations and may not perform their obligations as expected;

•

collaborators may deemphasize or not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus, including as a result of a business combination or sale or disposition of a business unit or development function, or available funding or external factors such as an acquisition that diverts resources or creates competing priorities;

•

collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing;

•

collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive products are more likely

•

to be successfully developed or can be commercialized under terms that are more economically attractive than ours;

•

a collaborator with marketing and distribution rights to multiple products may not commit sufficient resources to the marketing and distribution of our product relative to other products;

•

we may grant exclusive rights to our collaborators that would prevent us from collaborating with others;

•

collaborators may not properly obtain, maintain, defend or enforce our intellectual property rights or may use our proprietary information and intellectual property in such a way as to invite litigation or other intellectual property related proceedings that could jeopardize or invalidate our proprietary information and intellectual property or expose us to potential litigation or other intellectual property related proceedings;

•

disputes may arise between the collaborators and us that result in the delay or termination of the research, development or commercialization of our product candidates or that result in costly litigation or arbitration that diverts management attention and resources;

•

collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates;

•

collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner or at all;

•

collaborators may not provide us with timely and accurate information regarding development progress and activities under the collaboration or may limit our ability to share such information, which could adversely impact our ability to report progress to our investors and otherwise plan our own development of our product candidates;

•

collaborators may own or co-own intellectual property covering our products or product candidates that result from our collaborating with them, and in such cases, we would not have the exclusive right to develop or commercialize such intellectual property; and

•

a collaborator’s sales and marketing activities or other operations may not be in compliance with applicable laws resulting in civil or criminal proceedings.

•

the timing and results of INDs, preclinical studies and clinical trials of our product candidates or those of our competitors;

•

the success of competitive products or announcements by potential competitors of their product development efforts;

•

regulatory actions with respect to our products or product candidates or our competitors’ products or product candidates;

•

actual or anticipated changes in our growth rate relative to our competitors;

•

regulatory or legal developments in the United States and other countries, including changes in leadership at various federal departments and agencies as well as new legislation, executive, and administrative actions under the Biden administration;

•

developments or disputes concerning patent applications, issued patents or other proprietary rights;

•

the recruitment or departure of key personnel;

•

announcements by us or our competitors of significant acquisitions, strategic collaborations, joint ventures, collaborations or capital commitments;

•

actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts;

•

fluctuations in the valuation of companies perceived by investors to be comparable to us;

•

market conditions in the pharmaceutical and biotechnology sector;

•

changes in the structure of healthcare payment systems;

•

share price and volume fluctuations attributable to inconsistent trading volume levels of our shares;

•

announcement or expectation of additional financing efforts;

•

sales of our common stock by us, our insiders or our other stockholders;

•

expiration of market stand-off or lock-up agreements;

•

the impact of any natural disasters or public health emergencies, such as the COVID‑19 pandemic; and

•

general economic, political, industry and market conditions and instability (such as those created by the ongoing conflict between Ukraine and Russia, including, without limitation, sanctions against Russia imposed by the United States, the European Union and others).

•

the timing and cost of, and level of investment in, research and development activities relating to our programs, which will change from time to time;

•

our ability to enroll patients in clinical trials and the timing of enrollment;

•

the cost of manufacturing our current product candidates and any future product candidates, which may vary depending on FDA, EMA or other comparable foreign regulatory authority guidelines and requirements, the quantity of production and the terms of our agreements with manufacturers;

•

expenditures that we will or may incur to acquire or develop additional product candidates and technologies or other assets;

•

the timing and outcomes of preclinical studies and clinical trials for product candidates from our RAF and FGFR programs, and any product candidates from our research programs, or competing product candidates;

•

the need to conduct unanticipated clinical trials or clinical trials that are larger or more complex than anticipated;

•

competition from existing and potential future products that compete with our RAF or FGFR programs or any of our research programs, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners;

•

any delays in regulatory review or approval of product candidates from our RAF or FGFR programs, or any of our research programs;

•

the level of demand for any of our product candidates, if approved, which may fluctuate significantly and be difficult to predict;

•

the risk/benefit profile, cost and reimbursement policies with respect to our product candidates, if approved, and existing and potential future products that compete with our RAF or FGFR programs, or any of our research programs;

•

our ability to commercialize product candidates from our RAF or FGFR programs, or any of our research programs, if approved, inside and outside of the United States, either independently or working with third parties;

•

our ability to establish and maintain collaborations, licensing or other arrangements;

•

our ability to adequately support future growth;

•

potential unforeseen business disruptions that increase our costs or expenses;

•

future accounting pronouncements or changes in our accounting policies; and

•

the changing and volatile global economic and political environment.

•

being permitted to provide only two years of audited financial statements, in addition to any required unaudited interim financial statements, with correspondingly reduced “Management’s Discussion and Analysis of Financial Condition and Results of Operations” disclosure in our periodic reports;

•

not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act;

•

not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements;

•

reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements; and

•

exemptions from the requirements of holding nonbinding advisory stockholder votes on executive compensation and stockholder approval of any golden parachute payments not previously approved.

•

establish a classified board of directors so that not all members of our board are elected at one time;

•

permit only the board of directors to establish the number of directors and fill vacancies on the board;

•

provide that directors may only be removed “for cause” and only with the approval of two-thirds of our stockholders;

•

authorize the issuance of “blank check” preferred stock that our board could use to implement a stockholder rights plan (also known as a “poison pill”);

•

eliminate the ability of our stockholders to call special meetings of stockholders;

•

prohibit stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders;

•

prohibit cumulative voting;

•

authorize our board of directors to amend the bylaws;

•

establish advance notice requirements for nominations for election to our board or for proposing matters that can be acted upon by stockholders at annual stockholder meetings; and

•

require a super-majority vote of stockholders to amend some provisions described above.

•

any derivative action or proceeding brought on our behalf;

•

any action asserting a claim of breach of fiduciary duty;

•

any action asserting a claim against us arising under the DGCL, our amended- and restated certificate of incorporation or our amended and restated bylaws; and

•

any action asserting a claim against us that is governed by the internal-affairs doctrine.

Item 1B.

Unresolved Staff Comments.

Item 2.

Properties.

Item 3.

Legal Proceedings.

Item 4.

Mine Safety Disclosures.

Item 5.

Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.

Item 6.

[Reserved].

Item 7.

Management’s Discussion and Analysis of Financial Condition and Results of Operations

•

advance our RAF through clinical development and our FGFR program from discovery and preclinical development into and through clinical development;

•

advance the development of our other small molecule research programs, including our CDK12 inhibitor and next-generation programs for our product candidates;

•

expand our pipeline of product candidates through our own product discovery and development efforts;

•

seek to discover and develop additional product candidates;

•

seek regulatory approvals for any product candidates that successfully complete clinical trials;

•

establish a sales, marketing and distribution infrastructure to commercialize any approved product candidates and related additional commercial manufacturing costs;

•

implement operational, financial and management systems;

•

attract, hire and retain additional clinical, scientific, management and administrative personnel;

•

maintain, expand, protect and enforce our intellectual property portfolio, including patents, trade secrets and know how; and

•

operate as a public company.

•

expenses incurred in connection with the discovery, preclinical and clinical development of our product candidates, including under agreements with third parties, such as consultants and CROs;

•

the cost of manufacturing compounds for use in our preclinical and clinical studies, including under agreements with third parties, such as consultants and contract manufacturing organizations (CMOs); and

•

costs associated with consultants for chemistry, manufacturing and controls (CMC) development, regulatory, statistics and other services, including expenses for technology and facilities.

•

the timing and progress of preclinical and clinical development activities;

•

the number and scope of preclinical and clinical programs we decide to pursue;

•

our ability to maintain our current research and development programs and to establish new ones;

•

establishing an appropriate safety profile with IND-enabling toxicology studies;

•

successful patient enrollment in, and the initiation and completion of, clinical trials;

•

per subject trial costs;

•

the number of trials required for regulatory approval;

•

the countries in which the trials are conducted;

•

the length of time required to enroll eligible subjects and initiate clinical trials;

•

the number of subjects that participate in the trials;

•

the drop-out and discontinuation rate of subjects;

•

potential additional safety monitoring requested by regulatory authorities;

•

the duration of subject participation in the trials and follow-up;

•

the successful completion of clinical trials with safety, tolerability and efficacy profiles that are satisfactory to applicable regulatory authorities;

•

the receipt of regulatory approvals from applicable regulatory authorities;

•

the timing, receipt and terms of any marketing approvals and post-marketing approval commitments from applicable regulatory authorities;

•

the extent to which we establish collaborations, strategic partnerships or other strategic arrangements with third parties, if any, and the performance of any such third party;

•

obtaining and retaining research and development personnel;

•

establishing commercial manufacturing capabilities or making arrangements with CMOs;

•

development and timely delivery of commercial-grade drug formulations that can be used in our planned clinical trials and for commercial launch; and

•

obtaining, maintaining, defending and enforcing patent claims and other intellectual property rights.

		Years Ended December 31,								Increase (Decrease)
		2021				2020
		(in thousands)
External expenses:
RAF		$	23,436			$	11,930			$	11,506
FGFR			11,085				6,870				4,215
Other programs and other unallocated costs			10,859				4,346				6,513
Total external expenses			45,380				23,146				22,234
Internal expenses			21,786				6,091				15,695
Total research and development expenses		$	67,166			$	29,237			$	37,929

•

advance our RAF through clinical development and FGFR program from discovery and preclinical development into and through clinical development;

•

advance the development of our other small molecule research programs, including our CDK12 inhibitor;

•

expand our pipeline of product candidates through our own product discovery and development efforts;

•

seek to discover and develop additional product candidates;

•

seek regulatory approvals for any product candidates that successfully complete clinical trials;

•

establish a sales, marketing and distribution infrastructure to commercialize any approved product candidates and related additional commercial manufacturing costs;

•

implement operational, financial and management systems;

•

attract, hire and retain additional clinical, scientific, management and administrative personnel;

•

maintain, expand, protect and enforce our intellectual property portfolio, including patents, trade secrets and know how; and

•

operate as a public company.

•

the scope, timing, progress, results and costs of researching and developing our product candidates, and conducting preclinical studies and clinical trials;

•

the scope, timing, progress, results and costs of researching and developing other product candidates that we may pursue;

•

the costs, timing and outcome of regulatory review of our product candidates;

•

the costs of future activities, including product sales, medical affairs, marketing, manufacturing and distribution, for any of our product candidates for which we receive marketing approval;

•

the costs of manufacturing commercial-grade products and sufficient inventory to support commercial launch;

•

the revenue, if any, received from commercial sale of our products, should any of our product candidates receive marketing approval;

•

the cost and timing of attracting, hiring and retaining skilled personnel to support our operations and continued growth;

•

the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims;

•

our ability to establish and maintain collaborations, strategic partnerships or marketing, distribution, licensing or other strategic arrangements with third parties on favorable terms, if at all;

•

the extent to which we acquire or in-license other product candidates and technologies, if any;

•

the timing, receipt and amount of sales of, or milestone payments related to or royalties on, our current or future product candidates, if any; and

•

the costs associated with operating as a public company.

		Year Ended December 31,
		2021				2020
		(in thousands)
Net cash used in operating activities		$	(71,065	)		$	(30,181	)
Net cash used in investing activities			(180,574	)			(31,709	)
Net cash provided by financing activities			36,237				350,899
Net (decrease) increase in cash, cash equivalents and restricted cash		$	(215,402	)		$	289,009

•

Fair Value of Common Stock-Prior to our initial public offering, the estimated fair value of our common stock was determined by our board of directors as of the date of each option grant, with input from management, considering our most recently available third-party valuation of our common stock as well as our board of directors’ assessment of additional objective and subjective factors that it believed were relevant and which may have changed from the date of the most recent third-party valuation to the date of the grant.  Since the completion of our initial public offering, the fair value of each share of common stock underlying stock option grants is based on the closing price of our common stock on the Nasdaq Global Select Market as reported on the date of grant.

•

Expected Term-We have opted to use the “simplified method” for estimating the expected term of options, whereby the expected term equals the arithmetic average of the vesting term and the original contractual term of the option, which is generally 10 years.

•

Expected Volatility-Due to the limited trading history of our common stock, we have based our estimate of expected volatility on the historical volatility of a group of similar companies that are publicly traded. The historical volatility data was computed using the daily closing prices for the selected companies’ shares during the equivalent period of the calculated expected term of the stock-based awards. We will continue to apply this process until a sufficient amount of historical information regarding the volatility of our own stock price becomes available.

•

Risk-Free Interest Rate-The risk-free interest rates used are based on the U.S. Treasury yield in effect at the time of grant for zero-coupon U.S. treasury notes with maturities approximately equal to the expected term of the stock options.

•

Expected Dividend-To date, we have not issued any dividends and do not expect to issue dividends over the life of the options and therefore have estimated the dividend yield to be zero.

Item 7A.

Quantitative and Qualitative Disclosures About Market Risk.