Roivant Sciences Ltd. - Annual Report: 2023 (Form 10-K)

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

As of September 30, 2022 (the last business day of the registrant’s most recently completed second fiscal quarter), the aggregate market value of the registrant’s common shares, par value $0.0000000341740141 per share (the “Common Shares”) held by non-affiliates of the registrant was approximately $445.2 million, based on the closing price of the registrant’s common stock on The Nasdaq Global Market of $3.22 per share.

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Our limited operating history and the inherent uncertainties and risks involved in biopharmaceutical product development may make it difficult for us to execute on our business model and for you to assess our future viability. We have not generated significant revenue from our operations since inception, and there is no guarantee that we will do so in the future.

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We may never achieve or maintain profitability.

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We will require additional capital to fund our operations, and if we fail to obtain necessary financing, we may not be able to successfully market our products, acquire or in-license new products or product candidates, complete the development and commercialization of our products and product candidates and continue to pursue our drug discovery efforts.

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We have limited experience as a commercial company and the marketing and sale of VTAMA® (tapinarof) or any future products may be unsuccessful or less successful than anticipated.

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We may not be successful in our efforts to acquire or in-license new product candidates.

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Our drug discovery efforts may not be successful in identifying new product candidates.

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We face risks associated with the allocation of capital and personnel across our businesses.

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We face risks associated with the Vant structure.

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We face risks associated with potential future payments related to our products and product candidates.

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We may engage in strategic transactions that could impact our liquidity, increase our expenses and present significant distractions to our management.

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Clinical trials and preclinical studies are very expensive, time-consuming, difficult to design and implement and involve uncertain outcomes. We may encounter substantial delays in clinical trials, or may not be able to conduct or complete clinical trials or preclinical studies on the expected timelines, if at all.

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Certain of our products and product candidates are novel, complex and difficult to manufacture. We could experience manufacturing problems that result in delays in our development or commercialization programs or otherwise harm our business.

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We may encounter difficulties enrolling and retaining patients in clinical trials, and clinical development activities could thereby be delayed or otherwise adversely affected.

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The results of our preclinical studies and clinical trials may not support our proposed claims for our products or product candidates, or regulatory approvals on a timely basis or at all, and the results of earlier studies and trials may not be predictive of future trial results.

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Interim, top-line or preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

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Obtaining approval of a new drug is an extensive, lengthy, expensive and inherently uncertain process, and the FDA or another regulator may delay, limit or deny approval. If we are unable to obtain regulatory approval in one or more jurisdictions for any products or product candidates, our business will be substantially harmed.

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Our clinical trials may fail to demonstrate substantial evidence of the safety and efficacy of product candidates that we may identify and pursue for their intended uses, which would prevent, delay or limit the scope of regulatory approval and commercialization.

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Our products and product candidates may cause adverse effects or have other properties that could delay or prevent their regulatory approval, cause us to suspend or discontinue clinical trials, abandon further development or limit the scope of any approved label or market acceptance.

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We depend on the knowledge and skills of our senior leaders and may not be able to manage our business effectively if we are unable to attract and retain key personnel.

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We will need to expand our organization and may experience difficulties in managing this growth, which could disrupt operations.

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If we are unable to obtain and maintain patent and other intellectual property protection for our technology, products and product candidates or if the scope of the intellectual property protection obtained is not sufficiently broad, we may not be able to compete effectively in our markets.

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If the patent applications we hold or have in-licensed with respect to our products or product candidates fail to issue, if their breadth or strength of protection is threatened, or if they fail to provide meaningful exclusivity for our current and future products or product candidates, it could dissuade companies from collaborating with us to develop product candidates, and threaten our ability to commercialize our products. Any such outcome could have a materially adverse effect on our business. Our pending patent applications cannot be enforced against third parties practicing the technology claimed in such applications unless and until a patent issues from such applications.

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Patent terms and their scope may be inadequate to protect our competitive position on current and future products and product candidates for an adequate amount of time.

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If our performance does not meet market expectations, the price of our securities may decline.

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We have incurred and will continue to incur increased costs as a result of operating as a public company and our management has devoted and will continue to devote a substantial amount of time to new compliance initiatives.

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Our failure to timely and effectively implement controls and procedures required by Section 404(a) of the Sarbanes-Oxley Act could have a material adverse effect on our business.

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Anti-takeover provisions in our memorandum of association and bye-laws, as well as provisions of Bermuda law, could delay or prevent a change in control, limit the price investors may be willing to pay in the future for our Common Shares and could entrench management.

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Our largest shareholders own a significant percentage of our Common Shares and are able to exert significant control over matters subject to shareholder approval.

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Future sales, or the perception of future sales, of our Common Shares by us or our existing shareholders in the public market could cause the market price for our Common Shares to decline and impact our ability to raise capital in the future.

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our limited operating history and risks involved in biopharmaceutical product development;

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our limited experience as a commercial-stage company and ability to successfully commercialize VTAMA® (tapinarof);

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our ability to raise additional capital to fund our business on acceptable terms or at all;

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the fact that we will likely incur significant operating losses for the foreseeable future;

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our ability to acquire or in-license new product candidates;

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our ability to identify new product candidates through our discovery efforts;

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our Vant structure and the potential that we may fail to capitalize on certain development opportunities;

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the impact of public health outbreaks, epidemics or pandemics (such as the COVID-19 pandemic) on our business (including our clinical trials and preclinical studies), operations and financial condition and results;

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clinical trials and preclinical studies, which are very expensive, time-consuming, difficult to design and implement and involve uncertain outcomes;

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the novelty, complexity and difficulty of manufacturing certain of our products and product candidates, including any manufacturing problems that result in delays in development or commercialization of our products and product candidates;

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difficulties we may face in enrolling and retaining patients in clinical trials and/or clinical development activities;

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the results of our clinical trials not supporting our proposed claims for a product candidate;

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interim, top-line and/or preliminary data from our clinical trials changing as more data becoming available or data being delayed due to audit and verification processes;

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changes in product manufacturing or formulation that could lead to the incurrence of costs or delays;

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the failure of any third-party we contract with to conduct, supervise and monitor our clinical trials to perform in a satisfactory manner or to comply with applicable requirements;

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the fact that obtaining approvals for new drugs is a lengthy, extensive, expensive and unpredictable process that may end with our inability to obtain regulatory approval by the FDA or other regulatory agencies in other jurisdictions;

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the failure of our clinical trials to demonstrate substantial evidence of the safety and efficacy of our products and product candidates, including, but not limited to, scenarios in which our products and product candidates may cause adverse effects that could delay regulatory approval, discontinue clinical trials, limit the scope of approval or generally result in negative media coverage of us;

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our inability to obtain regulatory approval for a product or product candidate in certain jurisdictions, even if we are able to obtain approval in certain other jurisdictions;

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our ability to effectively manage growth and to attract and retain key personnel;

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any business, legal, regulatory, political, operational, financial and economic risks associated with conducting business globally;

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our ability to obtain and maintain patent and other intellectual property protection for our technology, products and product candidates;

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the inadequacy of patent terms and their scope to protect our competitive position;

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the failure to issue (or the threatening of their breadth or strength of protection) or provide meaningful exclusivity for our current and future products and product candidates of our patent applications that we hold or have in-licensed;

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the fact that we do not currently and may not in the future own or license any issued composition of matter patents covering certain of our products and product candidates and our inability to be certain that any of our other issued patents will provide adequate protection for such products and product candidates;

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the fact that our largest shareholders own a significant percentage of our stock and will be able to exert significant control over matters subject to shareholder approval;

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future sales of securities by us or our largest shareholders, or the perception of such sales, and the impact thereof on the price of our common shares;

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the outcome of any pending or potential litigation, including but not limited to our expectations regarding the outcome of any such litigation and costs and expenses associated with such litigation;

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changes in applicable laws or regulations;

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the possibility that we may be adversely affected by other economic, business and/or competitive factors; and

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any other risks and uncertainties, including those described under Part I, Item 1A. “Risk Factors.”

ITEM 1.

BUSINESS

Product/Product Candidate		Indication		Vant		Modality		Phase
VTAMA (tapinarof)		Psoriasis		Dermavant		Topical		Commercial
VTAMA (tapinarof)		Atopic Dermatitis		Dermavant		Topical		Phase 3*
RVT-3101		Ulcerative Colitis		Telavant		Biologic		Phase 3*
RVT-3101		Crohn’s Disease		Telavant		Biologic		Phase 2
Brepocitinib		Dermatomyositis		Priovant		Small Molecule		Phase 3*
Brepocitinib		Systemic Lupus Erythematosus		Priovant		Small Molecule		Phase 2*
Brepocitinib		Other Indications		Priovant		Small Molecule		Phase 2
Batoclimab		Myasthenia Gravis		Immunovant		Biologic		Phase 3*
Batoclimab		Thyroid Eye Disease		Immunovant		Biologic		Phase 3*
Batoclimab		Chronic Inflammatory Demyelinating Polyneuropathy		Immunovant		Biologic		Phase 2*
Batoclimab		Graves’ Disease		Immunovant		Biologic		Phase 2
IMVT-1401		Numerous Indications		Immunovant		Biologic		Phase 1
Namilumab		Sarcoidosis		Kinevant		Biologic		Phase 2*
RVT-2001		Transfusion-Dependent Anemia in Patients with Lower-Risk MDS		Hemavant		Small Molecule		Phase 1/2

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Leveraging complementary approaches to identify or discover promising drug candidates: We assembled our current development-stage product candidate pipeline by leveraging our business development expertise and vast network of industry relationships to relentlessly pursue opportunities to in-license or acquire programs where we believe we can deliver successful outcomes on accelerated timelines. In addition, our small molecule discovery engine allows us to design, optimize and validate our own novel product candidates, providing us with another avenue to pursue compelling targets or pathways and further expand our pipeline.

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Creating nimble, entrepreneurial Vants: Vants operate similarly to independent biotechnology companies where each management team is focused on its respective mission and is economically incentivized to maximize value through Vant-specific equity grants. Each of our Vant teams is built with deep relevant expertise to ensure successful execution of its particular development strategy. The Vant model is designed to facilitate rapid decision making and calculated risk taking, by empowering, aligning and incentivizing Vant teams around the outcomes of their specific products or product candidates.

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Developing and deploying proprietary technologies: We believe we are able to develop transformative medicines faster by building and applying computational tools to drug discovery, development and commercialization. We occupy a unique position at the intersection of biopharma and technology, having built our capabilities in parallel, optimizing each for synergy with the other, in contrast to big pharma who have added software tools to legacy workflows or technology startups that lack experience developing drugs. Vants have access to, and are supported by, these technologies.

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Allocating capital to maximize R&D efficiency: We apply an objective, rigorous decision framework across the drug development process designed to ensure resources and capital are continuously directed towards programs we believe have a higher probability of success and away from those that fail to meet our internal hurdles. We centralize capital allocation decisions at the Roivant level, while distributing operational decisions to the Vants, allowing us to strategically deploy capital in high growth areas, regardless of potentially competing operational priorities.

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Maintaining a diversified pipeline with various risk profiles: We have built a broad and differentiated pipeline that includes a commercial drug and several drug candidates across different therapeutic areas, phases of development, modalities and geographies. This approach limits our exposure to several concentrated scientific and biological risks and allows us to pursue multiple innovative hypotheses across our portfolio as we seek to develop therapies for patient populations with high unmet need.

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Designing creative “win-win” deal structures: We structure our partnerships to balance risk and the potential for future value creation. We ensure that a significant proportion of near-term expenses go toward development, allowing us to stage our investment and align incentives as well as limit losses in the event of a setback. Our scale and proven track record of developing successful product candidates assures partners that we are uniquely capable of maximizing value for patients and investors.

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Providing operating leverage through centralized support functions: Our model allows us to accelerate Vant formation and maturation by centralizing and sharing certain support functions across various Vants. Vants also benefit from access to our vast network of scientific experts, physicians and technologists to help optimize their clinical development and plans for commercialization.

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VTAMA

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Secured FDA approval of VTAMA® (tapinarof) cream, 1% for plaque psoriasis in adults, the Company’s first commercial product and first topical novel chemical entity for psoriasis in the U.S. in 25 years.

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Successfully launched with drug in channel within days of FDA approval and became the most prescribed branded topical for psoriasis only eight weeks into launch.

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Met the primary and all secondary endpoints in two Phase 3 studies, evaluating 813 moderate-to-severe atopic dermatitis patients with no new safety or tolerability signals observed in this population, which included children as young as 2 years old.

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Generated net product revenue of $13.7 million for the fourth quarter and $28.0 million for the fiscal year ended March 31, 2023.

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Expanded coverage with 125 million U.S. commercial lives covered, or 76% of total, as of June 2023.

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RVT-3101

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Announced partnership with Pfizer to form new company around RVT-3101, a potential first-in-class and best-in-class anti-TL1A antibody for ulcerative colitis and Crohn’s disease.

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Reported statistically significant and clinically meaningful results from the induction period of TUSCANY-2, a large global phase 2b study of subcutaneous RVT-3101 for the treatment of ulcerative colitis.

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Demonstrated improved efficacy results from the induction to chronic period in the TUSCANY-2 study and was well tolerated with a favorable safety profile across all doses.

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Initiated a Phase 2 study of RVT-3101 in Crohn’s disease, with topline data expected in the fourth quarter of calendar year 2024.

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Anti-FcRn Franchise

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Initiated a Phase 3 study of batoclimab in thyroid eye disease (“TED”) and a Phase 2b study in chronic inflammatory demyelinating polyneuropathy (“CIDP”).

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Unveiled IMVT-1402, a next generation anti-FcRn which showed deep IgG lowering similar to batoclimab with no or minimal impact observed on albumin and LDL (low-density lipoprotein) levels in animal studies.

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Initiated a Phase 1 study for IMVT-1402, with initial data expected in August / September 2023.

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Brepocitinib

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Announced Priovant Therapeutics, a new Vant partnered with Pfizer and dedicated to developing and commercializing novel therapies for autoimmune diseases with lead compound, brepocitinib, a first-in-class dual, selective inhibitor of TYK2 and JAK.

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Initiated a Phase 3 study developing oral brepocitinib for the treatment of dermatomyositis.

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Completed enrollment for its ongoing potentially registrational global study evaluating oral brepocitinib for the treatment of SLE in August 2022.

Vant		Product or Product Candidate		Milestones			Royalty
Dermavant		VTAMA (tapinarof)		•	Up to CAD$75M in remaining commercial milestones to Welichem, with CAD$35M payable upon VTAMA first U.S. commercial sale for atopic dermatitis and the remainder payable as first commercial sales are achieved in various ex-U.S. countries		•	Low single-digit to high single-digit tiered percentage of quarterly revenues based on achievement of specified net sales thresholds, up to a $344M cap, to be paid to an investor group in exchange for $160M RIPSA funding received in June 2022, following VTAMA approval; accounted for as debt with a net carrying value of $174M as of March 31, 2023
				•	Additional milestones owed to NovaQuest in connection with two 2018 financings that are accounted for as debt with a fair value of $208M as of March 31, 2023
Immunovant		Anti-FcRn Franchise		•	Up to a maximum of $432.5M (after an aggregate amount of $20.0M of milestone achievements as of March 31, 2023) upon the achievement of certain development, regulatory and sales milestone events		•	Tiered royalties on net sales ranging from mid-single digits to mid-teens
Telavant		RVT-3101		•	None		•	Mid-single-digit royalty on net sales
Priovant		Brepocitinib		•	Mid tens-of-millions sales milestone payment if aggregate net sales in a given year exceed a mid hundred-of-millions amount		•	Tiered sub-teens royalty on net sales
Kinevant		Namilumab		•	Up to $40M upon the achievement of certain milestones		•	Tiered royalties on net sales ranging from sub-teens to mid-teens
Hemavant		RVT-2001		•	Up to $65M in development and regulatory milestones for the first indication; up to $18M in payments for each additional indication; up to $295M in commercial milestone payments		•	Tiered high single-digit to sub-teens royalty on net sales

		Roivant Ownership
Vant		Basic1				Fully Diluted2
Dermavant			100	%			85	%
Immunovant			57	%3			51	%3
Telavant			75	%			75	%
Priovant			75	%			69	%
Proteovant			60	%			54	%
Genevant			83	%			65	%
Kinevant			96	%			90	%
Hemavant			100	%			99	%
Covant			100	%			93	%
Psivant			100	%			90	%
Arbutus			24	%3			21	%3
Lokavant			64	%			57	%
Datavant			*				*

1.

Basic ownership refers to Roivant’s percentage ownership of the issued and outstanding common and preferred shares (if applicable) of the entity.

2.

Fully diluted ownership refers to Roivant’s percentage ownership of all outstanding equity interests of the entity, including unvested RSUs as well as options and warrants, in each case whether vested or unvested.

3.

Denotes entities that are publicly traded.

*

As of March 31, 2023, the Company’s minority equity interest in Datavant represented approximately 17% of the outstanding Class A units. Datavant’s capital structure includes several classes of preferred units that, among other features, have liquidation preferences and conversion features. Upon conversion of such preferred units into Class A units, the Company’s ownership interest would be diluted. For more information on Roivant’s ownership interest in Datavant, please refer to Note 4 to Roivant’s audited consolidated financial statements included in this Annual Report on Form 10-K.

Program		Vant		Catalyst		Expected Timing
VTAMA (tapinarof) cream		Dermavant		Updates on commercial launch of VTAMA in psoriasis		Ongoing
Roivant pipeline growth		Roivant		New mid/late-stage in-licensing announcements		Ongoing
LNP platform		Genevant		Updates to LNP patent litigation		Ongoing
IMVT-1402		Immunovant		Initial data from Phase 1 trial (SAD results)		Aug./Sept. 2023
IMVT-1402		Immunovant		Initial data from Phase 1 trial (MAD results)		Oct./Nov. 2023
Brepocitinib		Priovant		Topline data from potentially registrational Phase 2B trial in systemic lupus erythematosus		4Q 2023
Batoclimab		Immunovant		Initial data from Phase 2 trial in Graves’ disease		4Q 2023
RVT-2001		Hemavant		Data from RVT-2001 Phase 1/2 trial in lower-risk myelodysplastic syndrome		2H 2023
VTAMA (tapinarof) cream		Dermavant		Expected sNDA filing for VTAMA in atopic dermatitis		1Q 2024
Batoclimab		Immunovant		Initial data from pivotal Phase 2B trial in chronic inflammatory demyelinating polyneuropathy		1H 2024
Namilumab		Kinevant		Topline data from Phase 2 trial in sarcoidosis		2H 2024
Batoclimab		Immunovant		Topline data from Phase 3 trial in myasthenia gravis		2H 2024
RVT-3101		Telavant		Topline data from induction portion of Phase 2 trial in Crohn's disease		4Q 2024
Batoclimab		Immunovant		Topline data from Phase 3 trials in thyroid eye disease		1H 2025
Brepocitinib		Priovant		Topline data from Phase 3 trial in dermatomyositis		2025

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Overview:

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Dermavant is marketing VTAMA® (tapinarof) cream, 1%, for the topical treatment of plaque psoriasis in adults. The FDA approved VTAMA for the topical treatment of mild, moderate, and severe plaque psoriasis in May 2022.

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Dermavant is also developing VTAMA for the treatment of atopic dermatitis in adults and children. We completed two Phase 3 clinical trials, ADORING 1 and ADORING 2 for the use of VTAMA in treating atopic dermatitis in adults and children. In both of these trials, VTAMA met its primary endpoint and secondary endpoints with clinically meaningful and statistically significant results.

•	Lead program:

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VTAMA is a novel, once daily, steroid-free topical cream approved in the US for the treatment of plaque psoriasis in adults. Dermavant is developing VTAMA for the treatment of atopic dermatitis in adults and children as young as 2 years old.

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VTAMA directly targets the AhR, a key regulator of skin homeostasis and inflammation.

•	Disease overview:

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Plaque psoriasis is a chronic, inflammatory disease of the skin characterized by lesions consisting of red patches and plaques with silvery scales.

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Atopic dermatitis, the most common type of eczema, is a chronic condition characterized by dry, itchy skin.

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Psoriasis and atopic dermatitis affect approximately 8 million and 26 million people in the United States, respectively.

•	Limitations of current treatment:

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Topical corticosteroids (“TCS”) are the most common first-line therapies but they typically cannot be used for longer than four weeks due to the risk of significant side effects.

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While oral and biologic therapies have become increasingly available, they are often limited to moderate-to-severe disease with often complicated access, reimbursement and utilization management requirements.

•	Clinical data:

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We completed two pivotal Phase 3 clinical trials, PSOARING 1 and PSOARING 2, for the use of VTAMA in treating mild, moderate, and severe plaque psoriasis in adults.

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In both pivotal Phase 3 trials, which enrolled over 500 patients each, VTAMA met its primary endpoint and secondary endpoints with clinically meaningful and statistically significant results.

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Our long-term open-label PSOARING 3 study provides evidence of VTAMA’s increased therapeutic effect beyond the 12-week double-blind treatment periods, suggesting treatment durability over time, as well as evidence of a remittive effect, measured by time until disease worsening following treatment discontinuation.

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In our pediatric maximal usage study of VTAMA in atopic dermatitis, VTAMA demonstrated favorable safety, pharmacokinetics and clinical improvement in atopic dermatitis in subjects as young as 2 years old.

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We recently reported top line data from two Phase 3 clinical trials, ADORING 1 and ADORING 2, for the use of VTAMA in treating atopic dermatitis in adults and children as young as 2 years old. In both of these trials, VTAMA met its primary endpoint and secondary endpoints with clinically meaningful and statistically significant results. The data indicated no new safety or tolerability signals in this population.

•	Development plan and upcoming milestones:

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The FDA approved VTAMA for the once daily topical treatment of adults with plaque psoriasis in May 2022, and we have built out our highly specialized commercial sales organization.

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VTAMA is the first topical novel chemical entity launched for plaque psoriasis in the U.S. in 25 years, offering a favorable mix of treatment effect, safety, tolerability, durability on therapy, and remittive effect.

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We expect to submit a supplemental new drug application to the FDA to approve VTAMA for the treatment of atopic dermatitis in adults and children in the first quarter of calendar year 2024.

•	Roivant ownership:

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As of March 31, 2023, we own 100% of the issued and outstanding common shares of Dermavant and 85% on a fully-diluted basis.

	TCS		Biologics		Orals; Injectables		Other Topicals
Annual Scripts for PsO (MAT April 2023)	~4.35M		~2.26M		~898K		~627K
Annual Scripts for AD (MAT April 2023)	~15.2M		~1.54M		~4.6M		~1.3M

	ADORING 1 Week 8			ADORING 2 Week 8
Endpoint	VTAMA 1% QD	Vehicle QD	P Value	VTAMA 1% QD	Vehicle QD	P Value
vIGA-AD success1	45.4%	13.9%	<0.0001	46.4%	18.0%	<0.0001
EASI752	55.8%	22.9%	<0.0001	59.1%	21.2%	<0.0001
≥4-point reduction in PP-NRS3	55.8%	34.2%	0.0366	52.8%	24.1%	0.0015

1

Primary Endpoint: Proportion of subjects who achieved a vIGA-AD score of clear (0) or almost clear (1) with at least a 2-grade improvement from baseline at Week 8.

2

Secondary Endpoint: Proportion of subjects with ≥75% improvement in EASI from baseline at Week 8.

3

Secondary Endpoint: Proportion of subjects ≥12 years old with a baseline PP-NRS score ≥4 who achieved ≥4-point reduction in the PP-NRS from baseline at Week 8.

•

Overview:

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Immunovant is developing a franchise of antibodies – batoclimab and IMVT-1402 – that target the neonatal fragment crystallizable receptor (“FcRn”), for the treatment of IgG-mediated autoimmune diseases.

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Programs:

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Batoclimab and IMVT-1402 are novel, fully human monoclonal antibodies that target FcRn.

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Both were designed to be optimized as a simple, self-administered subcutaneous (“SC”) injection with dosing that we believe can be tailored based on disease severity and stage.

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In nonclinical studies and in clinical trials conducted to date, batoclimab has been observed to reduce immunoglobulin G (“IgG”) antibody levels. High levels of pathogenic IgG antibodies drive a variety of autoimmune diseases and, as a result, we believe batoclimab has the potential for broad application in related disease areas.

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IMVT-1402 has also been observed in nonclinical studies to reduce IgG antibody levels. Importantly, based on the anticipated human effective dose levels, the human equivalent doses of IMVT-1402 have demonstrated minimal or no impact on levels of albumin and low-density lipoprotein (“LDL”) cholesterol in cynomolgus monkeys. This is a key attribute for IMVT-1402, which we believe could potentially allow its use as a treatment of chronic conditions requiring maintenance doses that achieve high degrees of IgG suppression.

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We are currently developing batoclimab for myasthenia gravis (“MG”), thyroid eye disease (“TED”), chronic inflammatory demyelinating polyneuropathy (“CIDP”) and Graves’ disease (“GD”), and we initiated a Phase 1 clinical trial of IMVT-1402 in the second quarter of calendar year 2023.

•	Disease overview:

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MG is a rare, chronic autoimmune disorder characterized by weakness and fatigue of voluntary muscles. The estimated prevalence of MG is 18 per 100,000, with up to 59,000 people in the U.S.

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TED is an autoimmune disorder affecting the tissues around the eyes, and in severe cases can be sight-threatening. TED has an estimated annual incidence of ten per 100,000 people in the U.S.

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CIDP is an autoimmune neurological disorder characterized by damage to the myelin sheaths or the nodes on nerve fibers of the peripheral nervous system. CIDP has an estimated prevalence of almost nine per 100,000 people in the US.

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GD is an autoimmune disorder associated with the overproduction of thyroid hormones and is the most common cause of hyperthyroidism. GD has an estimated incidence of 35 per 100,000 people in the US.

•	Limitations of current treatments:

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Early-stage disease: corticosteroids and immunosuppressants.

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Later-stage disease: intravenous immunoglobulin (“IVIg”), or plasma exchange.

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Approaches are limited by delayed onset of action, waning therapeutic benefit over time and unfavorable safety profiles.

•	Clinical data:

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In the highest dose cohorts in the Phase 1 clinical trial, four weekly SC administrations of 680 mg of batoclimab resulted in a mean maximum reduction of serum IgG levels of 78%, with a standard deviation of 2%. Injection site reactions were similar between batoclimab and placebo arms.

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As previously disclosed, we voluntarily paused dosing in our early phase clinical trials of batoclimab to evaluate treatment-induced elevations in total cholesterol and LDL levels observed in some trial subjects. After evaluation of the available safety data and following discussions with multiple regulatory authorities, we are continuing the clinical development of batoclimab.

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In 2019, we initiated an open-label, single-arm Phase 2a clinical trial of batoclimab for the treatment of TED. The majority of subjects (four of seven) evaluated at the end of treatment experienced a greater than or equal to 2-point improvement in clinical activity score (CAS) and three of seven subjects were proptosis responders, defined as a greater than or equal to 2mm reduction in proptosis in the study eye. In 2019, we also initiated a randomized, masked, placebo-controlled Phase 2b clinical trial of batoclimab for the treatment of TED. Our voluntary pause in dosing in February 2021 resulted in unblinding this trial and the primary endpoint was not significant. However, our analysis of exploratory endpoints from the Phase 2b trial, in addition to the findings from the Phase 2a trial, increased our confidence in the anti-FcRn mechanism of action for patients with TED, and they provide part of the basis for our interest in moving forward with further development in TED.

•	Development plan and upcoming milestones:

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We expect top-line data from the Phase 3 pivotal trial of batoclimab as a treatment for MG to be available in the second half of calendar year 2024.

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We expect top-line data from the Phase 3 clinical program of batoclimab as a treatment for TED to be available in the first half of calendar year 2025.

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We expect initial data from the open-label period of the pivotal Phase 2b trial of batoclimab as a treatment for CIDP (where one of two blinded doses of batoclimab are delivered) to be available in the first half of calendar year 2024.

•

We expect initial data from the proof-of-concept Phase 2 trial of batoclimab as a treatment for GD to be available in the fourth quarter of calendar year 2023.

•

We have initiated a Phase 1 trial of IMVT-1402 and expect initial data from single-ascending dose cohorts to be available in August or September 2023 and from multiple-ascending dose cohorts in October or November 2023.

•	Roivant ownership:

•

As of March 31, 2023 we own 57% of the issued and outstanding shares of Immunovant common stock and 51% on a fully diluted basis.

•

Three cohorts consisting of adult participants diagnosed with CIDP per European Academy of Neurology/Peripheral Nerve Society CIDP guidelines, 2021 revision. Randomized cohorts are defined by CIDP treatment at screening (i.e., Ig or PLEX, corticosteroid or no treatment).

•

Washout period of ≤ 12 weeks: Participants who fail to worsen by the end of the washout period will be withdrawn from the study.

•

Period 1 - Randomized Treatment (12 weeks): Two dose regimens include doses of 680 mg subcutaneous injection weekly (“QW SC”) or 340 mg QW SC. Non-responders who complete Period 1 will be withdrawn from the study after completing Week 12 and the subsequent 4-week follow-up visit.

•

Period 2 - Randomized Withdrawal (≤ 24 weeks): Includes doses of 340 mg QW SC or placebo.

•

Primary endpoint: Proportion of relapse events in Period 2 for patients receiving Ig or PLEX at time of screening (Cohort A).

•

Long Term Extension: Participants that relapse in Period 2 or complete Period 2 without relapse will be eligible for participation in the Long-term Extension Study. Participants without relapse will receive doses of 340 mg QW while those that relapse in Period 2 will receive an initial dose of 680 mg QW for 4 weeks followed by the 340 mg QW dose.

•

Overview:

•

Telavant is developing RVT-3101, a monoclonal antibody targeting tumor necrosis factor-like cytokine 1A (“TL1A”), for the treatment of inflammatory bowel disease (“IBD”), including ulcerative colitis (“UC”) and Crohn’s disease (“CD”), as well other inflammatory and fibrotic disorders.

•	Lead program:

•

RVT-3101 is a potentially first-in-class, fully human monoclonal antibody targeting TL1A. TL1A blockade is a novel, pleiotropic mechanism of action that inhibits the pathogenic amplification of multiple immune cell subsets, the production of proinflammatory cytokines and lowers markers of fibrosis that characterize IBD and numerous other immune and fibrotic diseases. RVT-3101 is Phase 3-ready in UC and Phase 2 in CD, with the potential to be the preferred treatment option and first precision therapy in moderate to severe IBD patients.

•	Disease overview:

•

Ulcerative colitis is a chronic inflammatory bowel disease characterized by relapsing and remitting mucosal inflammation. The inflammation is limited to the rectum and colon and is driven initially by either an epithelial cell or structural intestinal epithelial dysfunction. Associated symptoms include abdominal pain, diarrhea, urgency, tenesmus and incontinence. Patients with moderate to severe UC tend to be dependent on, or refractory to, corticosteroids and other treatments, including advanced therapies, have considerable endoscopic disease activity (presence of ulcers), and can be at high risk of colectomy.

•

Crohn’s disease is characterized by transmural inflammation which may involve any portion of the luminal gastrointestinal tract, and can extend from the perianal area to esophagus and even the oral cavity. The typical symptoms of CD include abdominal pain, diarrhea (with or without bleeding), fatigue and weight loss. CD can lead to the development of structural complications, including strictures (narrowing of the intestine), fistulas (tracts that connect the intestine to other organs) and abscesses. Strictures often lead to repeated episodes of abdominal pain and small bowel obstruction, or less commonly, colonic obstruction. CD is also associated with complications beyond the GI tract and patients show a heightened risk of colorectal and small bowel cancer.

•

IBD is an approximately $17 billion market in the U.S. alone and growing, with leading therapies generating over $15 billion in U.S. sales in 2022. We estimate that there are over two million patients in the U.S. that suffer from IBD, with UC and CD being the two most common forms.

•	Limitations of current treatments:

•

Poor prognostic indicators, limited efficacy, an unfavorable safety and tolerability profile and a lack of biomarkers lead to a “trial and error” treatment paradigm or the eventual removal of the colon for more severe IBD patients.

•

The treatment goal for patients with moderate to severe UC is to achieve remission, defined as durable clinical and endoscopic remission without corticosteroid therapy. Aminosalicylates (5-ASAs) are the preferred initial treatment option, followed by corticosteroids. Patients that do not respond adequately to steroid use or are unable to taper off without disease relapse then move onto advanced therapies, such as TNF, integrin, IL-12/23 or JAK inhibitors. Despite the approval of multiple classes of advanced therapies, the unmet need for patients to achieve remission is high. Remission rates remain below 30%, and many patients lose their response over time. Many of the existing treatment options do not offer both high-end efficacy and a favorable safety profile.

•

The treatment goal for patients with CD is to achieve and maintain remission as existing agents often struggle to maintain consistent efficacy throughout the lifetime of a patient. Corticosteroids and immunosuppressive medication are generally used as the initial treatment options. TNF inhibitors are the most used advanced therapies for moderate to severe patients, however, while they may be fast-acting and effective in the induction setting, they often drop off in efficacy in the maintenance settings. Other approved agents, such as integrin, IL-12/23, and JAK inhibitors have similar limitations, either due to safety or efficacy. A large unmet need still exists for CD patients for a safe and effective long-term treatment option. Additionally, remission rates in biologic experienced or inadequate responders can be modest, indicating a high unmet need in the second-line advanced setting. In addition, there can be fibrotic manifestations in CD which are particularly hard to treat, especially with available therapies.

•	Clinical data:

•

To date, clinical proof of concept has been demonstrated in ~300 patients across two Phase 2 (TUSCANY and TUSCANY-2) trials of RVT-3101 in UC supporting a Phase 3 program in a broad population of patients with moderate/severe active UC. Across all clinical studies more than 400 subjects have been dosed with RVT-3101.

•

TUSCANY-2 is a large, global, randomized, double-blind, placebo-controlled dose-ranging Phase 2b study to investigate the efficacy, safety and pharmacokinetics of RVT-3101 in adult participants with moderate to severe ulcerative colitis. TUSCANY-2 is a 56-week study in which the key efficacy and safety endpoints from the induction period comparing different doses of RVT-3101 against placebo were evaluated at week 14. Key outcomes for the chronic period, in which all patients were to receive RVT-3101, were evaluated at week 56. Patients who received RVT-3101 in the induction period were preassigned to receive either the same or a lower dose in the chronic period.

•

After the induction period of TUSCANY-2 (Week 14), RVT-3101 demonstrated statistically significant and clinically meaningful rates of clinical remission and endoscopic improvement versus placebo at each dose tested. Biomarker positive patients achieved higher clinical remission and endoscopic improvement compared to all-comers.

1.

In ~20% of patients across the study, biomarker was not analyzed due to lack of consent at specific sites.

2.

Among patients for whom biomarker status was analyzed, biomarker positive or negative status was determined in 100% of patients.

3.

One-sided p-value of difference of proportions were computed using Chan And Zhang (1999) method, in accordance with Pfizer’s prespecified statistical analysis plan. Statistical significance considered to be a p-value ≤ 0.025.

4.

Placebo-adjusted delta values may not exactly match the difference between gross and placebo values due to rounding.

•

At the expected Phase 3 dose of RVT-3101, statistically significant and clinically meaningful improvements in clinical remission and endoscopic improvement beyond those seen in the overall population were observed.

•	Development plan and upcoming milestones:

•

We have initiated a Phase 2 dose-ranging study of RVT-3101 in patients with CD. We expect topline data from the induction period to be available in the fourth quarter of calendar year 2024.

•

As of March 31, 2023, we own 75% of the issued and outstanding shares of Telavant and 75% on a fully diluted basis.

•

Overview:

•

Genevant is a technology-focused nucleic acid delivery and development company with two delivery platforms—a lipid nanoparticle (“LNP”) platform and a ligand conjugate platform—an expansive intellectual property portfolio and deep scientific expertise, currently focused on partnering with other pharmaceutical or biotechnology companies to enable the development of nucleic acid therapeutics for unmet medical needs.

•	Delivery platforms:

•

Genevant has two delivery platforms: LNP and ligand conjugate.

•

LNP platform:

•

Proven technology as demonstrated by head-to-head in vivo ionizable lipid study assessing LNP potency and immune stimulation

•

Clinically validated for hepatocyte and vaccine applications and in various stages of development for other traditionally hard-to-reach tissues and cell types, including lung, eye, central nervous system, and hepatic stellate and immune cells

•

Over 650 issued patents and pending patent applications as of March 31, 2023

•

Ligand conjugate platform:

•

Novel GalNAc ligands with demonstrated ability to deliver to the liver in preclinical studies

•

In preclinical head-to-head testing, demonstrated equal or better preclinical potency, assessed by duration and magnitude of knockdown, compared to a current industry benchmark

•

Applying delivery expertise to design novel extrahepatic ligands to expand therapeutic reach

•	Collaboration-based business model:

•

Genevant uses its expertise in the delivery of nucleic acid therapeutics to develop optimal delivery systems for its collaborators’ identified payloads or target tissues.

•

Genevant collaboration-based business model is to seek some or all of upfront payments, R&D reimbursements, and milestones and royalties (or profit share) upon success, while also retaining certain rights in the delivery-related intellectual property developed in the context of the collaboration for potential use or out-license.

•

Some current collaboration partners include BioNTech, Takeda, Sarepta, Gritstone, ST Pharm, 2seventy bio, Korro Bio, Chulalongkorn University (through its Vaccine Research Center) and Providence Therapeutics.

•	Clinical data:

•

Genevant LNP technology has been in clinical testing in over a dozen distinct product candidates, representing hundreds of subjects of clinical experience.

•

Genevant LNP technology is included in the first RNA-LNP product to receive FDA-approval, Alnylam’s Onpattro (patisiran).

•	Roivant ownership:

•

As of March 31, 2023, we own 83% of the issued and outstanding common shares of Genevant and 65% on a fully diluted basis.

•

Contains intrinsic endosomolytic properties

•

Has demonstrated marked in vivo enhancement in potency

•

Has maintained a subcutaneous dosing regimen and is expected to be dosed subcutaneously in clinical trials

•

Remains compatible with other ligand types

•

Access to validated technology to deliver nucleic acid therapeutics for hepatocyte or vaccine applications

•

Potential to deliver RNA payloads to historically challenging-to-reach tissue or cell types, as well as nucleic acid design capabilities

•

No need to build internal delivery expertise or build intellectual property estate from scratch in an increasingly complex field

•

Opportunity to expand core delivery technology and capabilities, maintaining leadership position in nucleic acid delivery

•

Typically, the ability to exploit certain rights to delivery-related intellectual property developed in the context of collaboration ourselves or with other collaborators

•

Opportunity to generate revenue through deal structures including some combination of upfront payments, R&D reimbursements and additional milestones and royalties upon successful outcomes

•

Gritstone—Access to Genevant’s LNP technology for use in Gritstone’s self-amplifying RNA COVID-19 vaccine program

•

Gritstone—Access to LNP technology for use with self-amplifying RNA for an unspecified indication

•

Sarepta—Research collaboration and option agreement for the delivery of LNP-gene editing therapeutics for specified neuromuscular diseases; Genevant will design and collaborate with Sarepta in the development of muscle targeted LNPs to be applied to gene editing targets in multiple indications, including Duchenne muscular dystrophy

•

BioNTech—Co-development in up to five rare diseases with high unmet medical need, and access to LNP technology for use with BioNTech’s mRNA for a specified number of oncology targets

•

Takeda—Access to LNP technology to develop nucleic acid therapeutics directed to specified targets in HSC to treat liver fibrosis

•

2seventy bio—Access to LNP technology to develop gene editing therapies for hemophilia A

•

Korro bio—Access to LNP technology to develop an RNA editing therapy for Alpha-1 Antitrypsin Deficiency

•

ST Pharm—Access to Genevant’s LNP technology for use in specified territories in ST Pharm’s mRNA COVID-19 vaccine program

•

Providence—Access to Genevant’s LNP technology for use in Providence’s mRNA COVID-19 vaccine program

•

Chulalongkorn University—Access to LNP technology for use in specified Asian territories in its mRNA COVID-19 vaccine program

•

lipid structures, including cationic and PEG-lipids

•

particle compositions, including commonly used ranges of lipid ratios for nucleic acid-containing particles

•

nucleic acid-containing particles with certain structural characteristics

•

mRNA-containing LNP formulations

•

various aspects of our manufacturing process

•

Overview:

•

Priovant is developing brepocitinib, a potent small molecule inhibitor of TYK2 and JAK1, for the treatment of dermatomyositis (“DM”), systemic lupus erythematosus (“SLE”) and other immune-mediated diseases.

•	Lead program:

•

Brepocitinib is a potentially first-in-class, orally administered, small molecule inhibitor of TYK2 and JAK1 that suppresses signaling of TYK2- and JAK1-dependent cytokines linked to autoimmunity, including type I and type II interferon, IL-6, IL-12, and IL-23.

•	Disease overview:

•

DM is a chronic, immune-mediated disease of the skin and muscles. Patients with DM usually present with a characteristic skin rash and proximal muscle weakness, which may lead to significant functional impairment or disfigurement. Patients with DM are at a substantially increased risk of interstitial lung disease, malignancy, and heart failure, contributing to an estimated 5-year mortality rate of 10-40%.

•

SLE is a chronic, immune-mediated connective tissue disease that can impact nearly all major organ systems. The most common manifestations of SLE are cutaneous and musculoskeletal symptoms, although neurological, gastrointestinal, hematological, and renal symptoms are regularly observed as well. Patients with SLE are at a substantially increased risk of infection and cardiovascular disease, contributing to estimated 10- and 15-year mortality rates of 9% and 15%, respectively.

•

We estimate that there are approximately 37,000 adult DM patients and up to 300,000 adult SLE patients in the US.

•	Limitations of current treatments:

•

Corticosteroids, disease-modifying antirheumatic drugs (“DMARDs”), and immunosuppressants, administered alone or in combination, are traditional therapies for patients with DM and SLE. Many of these therapies are associated with significant toxicities and limited efficacy.

•

For patients with DM who do not respond adequately to traditional therapies, IVIg (OCTAGAM 10%) is an important FDA-approved treatment. However, clinical trial data from the Phase 3 ProDERM study of IVIg in patients with DM and case reports from years of prior off-label use confirm that even with IVIg, many patients with DM continue to suffer from residual disease activity. Moreover, IVIg administration is burdensome, typically requiring several hours of infusion therapy for multiple days each month. IVIg also has a black box warning for serious risks, including thrombosis and kidney failure.

•

For patients with SLE who do not respond adequately to traditional therapies, belimumab (BENLYSTA) and anifrolumab (SAPHNELO) are FDA-approved biologic treatments. However, in each of belimumab’s BLISS Phase 3 program and anifrolumab’s TULIP Phase 3 program, the clinical trial data demonstrates that many patients failed to respond to these therapies, and both therapies are administered intravenously or subcutaneously.

•	Clinical data:

•

Brepocitinib has been evaluated in five completed placebo-controlled Phase 2 studies in immune-mediated diseases (psoriatic arthritis, plaque psoriasis, ulcerative colitis, alopecia areata, and hidradenitis suppurativa). In all five of these studies, treatment with brepocitinib was associated with statistically significant and clinically meaningful efficacy.

Study Population		N1		Brepocitinib Dose		Primary Endpoint Result		Statistical Significance
Psoriatic Arthritis		218		30 mg once daily		23.4% placebo-adjusted ACR20 RR at week 16		P = 0.0197
Plaque Psoriasis		212		30 mg once daily		-10.1 placebo-adjusted CFB in PASI score at week 12		P < 0.0001
Ulcerative Colitis		167		30 mg once daily		-2.28 placebo-adjusted CFB in Mayo Score at week 8		P = 0.0005
Alopecia Areata		942		30 mg once daily3		49.18 placebo-adjusted CFB in SALT Score at week 24		P < 0.00014
Hidradenitis Suppurativa		100		45 mg once daily5		18.7% placebo-adjusted HiSCR rate at week 16		P = 0.02984

1.

Overall study N represents patients randomized to all brepocitinib dose levels or placebo and excludes patients randomized to other agents.

2.

Includes patients from initial 24-week study period only.

3.

60 mg once daily for 4 weeks followed by 30 mg once daily for 20 weeks.

4.

One-sided p-value (pre-specified statistical analysis).

5.

Brepocitinib 45 mg once daily was the only dose evaluated in this study.

•

Brepocitinib’s safety database includes over 1,400 exposed participants evaluated in 14 completed Phase 1 and Phase 2 studies and three ongoing Phase 1 and Phase 2 studies. In these studies, brepocitinib was generally safe and well-tolerated, and rates of JAK class treatment-emergent adverse events (“TEAEs”) of interest were comparable to those observed in the development programs of approved JAK inhibitors. Collectively, these data suggest a safety profile that is similar to those of approved JAK inhibitors.

•

Brepocitinib has not been evaluated in DM to date. However, several FDA-approved JAK inhibitors have been clinically validated in DM patients refractory to standard-of-care therapies, as reported in more than 100 off-label case reports and in an open-label clinical trial. In addition, since DM pathobiology is driven by dysregulations in cytokines whose signaling is mediated by both TYK2 and JAK1, we believe that, with its unique dual inhibition of both TYK2 and JAK1, brepocitinib, as compared to inhibitors selective to either TYK2 or JAK1 has the potential to demonstrate superior clinical efficacy in DM.

•

Brepocitinib has not been evaluated in SLE to date. However, FDA-approved and investigational JAK inhibitors have completed successful proof-of-concept studies in SLE patients. And, like DM, SLE pathobiology is driven by dysregulations in cytokines whose signaling is mediated by both TYK2 and JAK1. We believe that, with its unique dual inhibition of both TYK2 and JAK1, brepocitinib, as compared to inhibitors selective to either TYK2 or JAK1, has the potential to demonstrate superior clinical efficacy in SLE.

•	Development plan and upcoming milestones:

•

Priovant is currently conducting a large randomized, controlled Phase 3 study of brepocitinib in patients with refractory dermatomyositis. This study will enroll approximately 225 subjects in total and will evaluate 15 mg and 30 mg of brepocitinib once-daily compared to placebo. The primary endpoint of this study is the mean Total Improvement Score (“TIS”), a validated myositis improvement index, at Week 52.

•

Brepocitinib is currently being evaluated in a large, randomized controlled Phase 2B study in patients with moderate to severe active SLE. This study is fully enrolled with 350 subjects in total and will evaluate 15 mg, 30 mg, and 45 mg of brepocitinib once-daily compared to placebo. The primary endpoint of this study is the Systemic Lupus Erythematosus Responder Index (“SRI-4”), a validated SLE improvement index, at Week 52. Priovant anticipates receiving topline results from this study in the second half of 2023.

•

Priovant is also evaluating brepocitinib for development in other orphan and specialty immune-mediated diseases.

•

As of March 31, 2023, we own 75% of the issued and outstanding shares of Priovant and 69% on a fully diluted basis.

•

Overview:

•

Hemavant is developing RVT-2001, a small molecule SF3B1 modulator, for the treatment of transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes (“MDS”).

•	Lead program:

•

RVT-2001 is a potentially first-in-class, orally administered, small molecule SF3B1 modulator that corrects SF3B1 mutation-induced splicing defects in mRNA transcripts that encode proteins thought to be associated with the development of MDS.

•	Disease overview:

•

Myelodysplastic syndromes are a group of hematologic malignancies in which immature blood cells in the bone marrow do not mature and become healthy blood cells. MDS patients are at risk for symptoms related to anemia, infection and bleeding, and they have variable survival expectations and rates of progression to acute myeloid leukemia (“AML”). Assessment of prognosis is a key aspect in selecting therapy for the patient with MDS, and prognostic models broadly differentiate patients into either lower-risk MDS or higher-risk MDS.

•

We believe that there are approximately 115,000 MDS patients in the US, with approximately 17,000 new MDS cases per year, two thirds of which are lower-risk MDS.

•	Limitations of current treatments:

•

Chronic anemia in patients with MDS requires regular and repeated red blood cell (“RBC”) transfusions, creating a significant burden for patients and an increased risk of organ toxicity from iron overload.

•

One of the primary goals of treatment is to reduce or eliminate RBC transfusion dependence while minimizing treatment-related toxicity. The first line of treatment for most lower-risk MDS patients consists of erythropoiesis-stimulating agents (“ESAs”), which are ineffective in over 50% of patients.

•

For patients who fail ESAs, the available treatment options depend on mutational status and disease phenotypes. In 2020, Reblozyl (luspatercept) became the only FDA-approved therapy for lower-risk MDS patients who are ring sideroblast positive and who have failed an ESA. Although Reblozyl can lead to transfusion independence, it is ineffective in over 50% of second line patients and is most effective in patients with a low transfusion burden. Reblozyl is delivered as an injection and is associated with numerous adverse events, including fatigue, a significant concern for patients already experiencing fatigue from anemia.

•	Clinical data:

•

In the dose-escalation portion of an ongoing Phase 1/2 study, over 30% (6/19) of patients with lower-risk, transfusion-dependent MDS treated with RVT-2001 became RBC-transfusion independent (“RBC-TI”), with a median duration of treatment of approximately two years for responders. The dose-escalation portion of the study was conducted in a highly refractory patient population, which we believe may have decreased the observed treatment response relative to what would be expected in a less refractory target population.

•

In the dose-escalation portion of this ongoing Phase 1/2 study, which had a total of 84 patients with AML, chronic myelomonocytic leukemia or MDS, RVT-2001 was observed to be generally well-tolerated, with the majority of events being classified as Grade 1.

•	Development plan and upcoming milestones:

•

We are currently conducting the dose-optimization portion of the ongoing open-label Phase 1/2 trial. The dose-optimization cohort includes only lower-risk MDS patients. We are also excluding patients with prior exposure to lenalidomide or hypomethylating agents, thereby enrolling a less refractory patient population in the dose-optimization cohort than the population from which the first 19 lower-risk, transfusion-dependent MDS patients were drawn during the dose-escalation portion. We are targeting a genetically defined subpopulation by enrolling only lower-risk MDS patients with SF3B1 mutations. In addition, we are evaluating baseline expression of TMEM14C transcripts as a potential biomarker predictive of response to RVT-2001, since among the 7 MDS patients with the highest levels of aberrant TMEM14C transcripts in the dose-escalation portion of this Phase 1/2 trial, 71% (5/7) became RBC-TI. We also aim to strengthen the phamacodynamic effect by optimizing the dose and schedule of RVT-2001. We expect data from the dose-optimization cohort of the Phase 1/2 trial in the second half of calendar year 2023.

•

We plan to position RVT-2001 initially as second line therapy in SF3B1-mutated patients, with the potential to expand to other spliceosome mutations and ultimately first line treatment.

•

The below schematic shows the trial design for the dose-optimization cohort of our ongoing Phase 1/2 study:

•	Roivant ownership:

•

As of March 31, 2023, we own 100% of the issued and outstanding common shares of Hemavant and 99% on a fully diluted basis.

•

Overview:

o

Kinevant is focused on developing namilumab for sarcoidosis and potentially other diseases.

•	Lead program:

o

Namilumab is a fully human anti-GM-CSF monoclonal antibody with broad potential in inflammatory and autoimmune diseases being developed with potentially the least frequent dosing schedule among subcutaneous anti-GM-CSFs in Phase 2 clinical trial, with a single dose every four weeks after an initial loading period.

•	Disease overview:

o

Sarcoidosis is a multi-system inflammatory disease characterized by the presence of non-necrotizing granulomas believed to be formed by an exaggerated immune response to unidentified antigens. Sarcoidosis primarily affects the lungs and lymphatic system, though sarcoidosis may damage any organ. GM-CSF, a key pathogenic cytokine, has been implicated in multiple parts of the granulomatous response.

o

Sarcoidosis affects approximately 200,000 people in the United States, with over 90% of cases presenting with pulmonary involvement.

o

An estimated 54% of pulmonary sarcoidosis patients are diagnosed, and approximately 90% of these patients receive some form of treatment. Market research with HCPs and third-party analysis of claims data suggest that approximately 25% of diagnosed and treated pulmonary sarcoidosis would be eligible for treatment with second-line or later therapy.

•	Limitations of current treatments:

o

Corticosteroids are the most widely used treatment for sarcoidosis, but they carry significant side effects when used longer-term. Second- and third-line treatment options, including immunosuppressive therapies and biologics, are limited by slow onset, safety risk, inconsistent effectiveness, and reimbursement challenges, leaving significant unmet medical need that could be met by a novel biologic.

•	Clinical data:

o

Early clinical data in pharmacokinetic/pharmacodynamic (PK/PD) and subsequent Phase 2 studies showed namilumab to be well-tolerated with a single subcutaneous injection given up to every four weeks.

o

In a Phase 1 study of healthy volunteers with a single subcutaneous injection, namilumab was observed to be generally well-tolerated.

o

In a Phase 2 trial in patients with moderate to severe rheumatoid arthritis conducted by Takeda, namilumab demonstrated decreased disease activity compared to placebo. In this trial, patients were given a subcutaneous injection of either 20, 80, or 150 mg of namilumab four times over a ten-week period. Over the 12-week study period, 14 of 27 (52%) subjects receiving placebo and 45 of 81 (56%) receiving namilumab experienced a treatment-emergent adverse event (TEAE). The most common TEAEs were nasopharyngitis, dyspnea, bronchitis, and headache.

•	Development plan and upcoming milestones:

o

We have initiated a Phase 2 trial to evaluate the safety and efficacy of namilumab in pulmonary sarcoidosis, with data expected in the first half of 2024.

•	Roivant ownership:

o

As of March 31, 2023, we own 96% of the issued and outstanding common shares of Kinevant, and 90% on a fully diluted basis.

•

Overview:

•

Proteovant is focused on the discovery and development of a robust pipeline of protein degraders targeting indications in oncology and immunology.

•	Protein degradation:

•

Protein degraders are a novel class of small molecules that target and destroy cellular proteins, rather than inhibiting them. Degraders are engineered to induce the degradation of specific disease-causing proteins through the ubiquitin-proteasome system, which ordinarily tags and degrades proteins that have been misfolded or have already fulfilled their biological function.

•

We believe degraders represent a promising new approach to drug previously “undruggable” targets and transform the treatment of diseases with significant unmet medical need.

•	Proteovant’s degrader strategy:

•

Proteovant is positioned for leadership in the field of targeted protein degradation given its long-term sponsored research agreement (“SRA”) with a leading academic lab, its internal R&D capabilities, as well as degrader-specific machine learning capabilities.

•

Proteovant has assembled a world-class team of scientists and drug developers with deep drug hunting capabilities in the field of small molecule degrader development to support its internal degrader discovery and development efforts. The core skill sets of the Proteovant team span all aspects of drug discovery and development, including medicinal chemistry, biology and structural biology, which is also supported by access to next generation wet labs.

•

Pipeline:

•

Proteovant has a broad pipeline of programs across oncology and immunology indications, and its protein degrader structures include hererobifunctionals and molecular glues. The protein degraders in Proteovant’s pipeline range from early target validation through later stages of preclinical development. Select targets include ER, IKZF2, STAT3, CBP/p300, and SMARCA2/4.

•	Roivant ownership:

•

As of March 31, 2023, we own 60% of the issued and outstanding common shares of Proteovant and 54% on a fully diluted basis.

•

Lokavant is a clinical trial intelligence platform that optimizes time, cost and quality of trial planning and execution through predictive analytics

•

Covant is developing covalent small molecules for historically intractable targets

•

Psivant uses its proprietary QUAISAR platform, integrating advanced computation and wet lab techniques, to accelerate the design of novel small molecule therapeutics for complex targets in oncology and immunology

•

VantAI is building a geometric deep learning platform for induced proximity drug discovery

•

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

•

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

•

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

•

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

•

submission to the FDA of an NDA or BLA;

•

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

•

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

•

potential FDA inspection of the clinical trial sites that generated the data in support of the NDA or BLA and/or us as the sponsor;

•

payment of user fees for FDA review of the NDA or BLA (unless a fee waiver applies);

•

agreement with FDA on the final labeling for the product and the design and implementation of any required REMS; and

•

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

•

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, side effect tolerability and safety of the product candidate.

•

Phase 2 clinical trials involve studies in disease-affected patients to evaluate proof of concept and/or determine the dose required to produce the desired benefits. At the same time, safety and further PK and PD 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, its safety in use and to establish the overall benefit/risk relationship of the product and provide an adequate basis for product labeling.

•

restrictions on the marketing or manufacturing of the drug or biologic, suspension of the approval, complete withdrawal of the drug from the market or product recalls;

•

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

•

refusal of the FDA to approve applications or supplements to approved applications, or suspension or revocation of drug or biologic approvals;

•

drug or biologic seizure or detention, or refusal to permit the import or export of drugs;

•

injunctions or the imposition of civil or criminal penalties; or

•

debarment from producing or marketing drug products or biologics.

•

made several changes to the Medicaid Drug Rebate Program, including increasing pharmaceutical manufacturers’ rebate liability by raising the minimum basic Medicaid rebate on most branded prescription drugs to 23.1% of average manufacturer price (“AMP”), and adding a new rebate calculation for “line extensions” (i.e., new formulations, such as extended release formulations) of solid oral dosage forms of branded products, as well as potentially impacting their rebate liability by modifying the statutory definition of AMP.

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imposed a requirement on manufacturers of branded drugs to provide a 70% (increased pursuant to the Bipartisan Budget Act of 2018, effective as of 2019) point-of-sale discount off the negotiated price of branded drugs dispensed to Medicare Part D beneficiaries in the coverage gap (i.e., “donut hole”) as a condition for a manufacturer’s outpatient drugs being covered under Medicare Part D.

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extended a manufacturer’s Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations.

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expanded the entities eligible for discounts under the 340B Drug Discount Program.

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established a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected.

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imposed an annual, nondeductible fee on any entity that manufactures or imports certain branded prescription drugs, apportioned among these entities according to their market share in certain government healthcare programs.

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established a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research. The research conducted by the Patient-Centered Outcomes Research Institute may affect the market for certain pharmaceutical products. The ACA established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

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The centralized MA is issued by the European Commission through the centralized procedure, based on the opinion of the Committee for Medicinal Products for Human Use (the “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 medicinal products (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 EEA.

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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. If a product is to be authorized in more than one Member State, the assessment procedure is coordinated between the relevant EU Member States. Where a product has already been authorized for marketing in a Member State of the EEA, the 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 (the “RMS”). The competent authority of the RMS coordinates the preparation of a draft assessment report, a draft summary of the product characteristics (the “SmPC”), and a draft of the labeling and package leaflet, which are sent to the other Member States (referred to as the Concerned Member States) for their final approval. If the Concerned Member States raise no objections, based on a potential serious risk to public health, to the assessment, SmPC, labeling, or packaging circulated by the RMS, the coordinated procedures is closed, and the product is subsequently granted a national MA in all the Member States (i.e., in the RMS and the Concerned Member States).

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Hire diverse, multidisciplinary talent across seniority levels with backgrounds represented from industries within and outside of biopharma with an in-house talent acquisition team

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Invest in early career diversity by recruiting a robust Roivant Analyst (RA) program for recent college graduates with representation from top private and public institutions

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Offer highly competitive short- and long-term incentives through both Roivant and Vant equity programs and meaningful performance-based bonuses

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Undertake rigorous analysis in partnership with third parties to ensure best compensation practices including internal and external benchmarking and yearly gender pay gap analyses

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Unlock unique career progression across Roivant and Vants through “Vant mobility” and offer unparalleled leadership opportunities for employees through the Vant model

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Cultivate diversity and inclusion among our employee base through Employee Resource Groups (ERGs), including Women@Roivant (Roivant’s women’s employee resource group), ROI-GBIV (Roivant’s LGBTQ+ employee resource group), and BIPOC (Roivant’s black, indigenous and people of color employee resource group)

ITEM 1A.

RISK FACTORS

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successfully continue to commercialize VTAMA;

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identify new acquisition or in-licensing opportunities;

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successfully complete ongoing preclinical studies and clinical trials and obtain regulatory approvals for our current and future products and product candidates;

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successfully identify new product candidates through our discovery efforts and advance those product candidates into preclinical studies and clinical trials;

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successfully grow our healthcare technology Vants and market the products and services offered by those Vants;

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raise additional funds when needed and on terms acceptable to us;

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attract and retain experienced management and advisory teams;

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add operational, financial and management information systems and personnel, including personnel to support clinical, preclinical manufacturing and commercialization efforts and operations;

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launch commercial sales of future product candidates, whether alone or in collaboration with others, including establishing sales, marketing and distribution systems;

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initiate and continue relationships with third-party suppliers and manufacturers and have commercial quantities of products and product candidates manufactured at acceptable cost and quality levels and in compliance with FDA and other regulatory requirements;

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set acceptable prices for products and product candidates and obtain coverage and adequate reimbursement from third-party payors;

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achieve market acceptance of products and product candidates in the medical community and with third-party payors and consumers; and

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maintain, expand and protect our intellectual property portfolio.

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the time and costs necessary to complete our ongoing, planned and future clinical trials;

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the time and costs necessary to pursue regulatory approvals for our current and future product candidates;

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the costs associated with future acquisitions or in-licensing transactions;

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the approval, progress, timing, scope and costs of our preclinical studies, clinical trials and other related activities, including the ability to enroll patients in a timely manner for our ongoing and planned clinical trials and potential future clinical trials;

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the costs associated with our ongoing, planned and future preclinical studies and other drug discovery activities;

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our ability to successfully identify and negotiate acceptable terms for third-party supply and contract manufacturing agreements with contract manufacturing organizations (“CMOs”);

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the costs of obtaining adequate clinical and commercial supplies of raw materials and drug products for our products and product candidates;

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our ability to successfully commercialize VTAMA, including:

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the manufacturing, selling and marketing costs associated with VTAMA, including the cost and timing of expanding sales and marketing capabilities or entering into strategic collaborations with third parties; and

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the amount and timing of sales and other revenues from VTAMA, including the sales price and the availability of adequate third-party reimbursement;

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the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights, including current and future patent infringement actions brought against third parties;

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the cost of pursuing and defending potential intellectual property disputes, including patent infringement actions with third parties relating to our current or future products or product candidates; and

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our ability to hire, attract and retain qualified personnel.

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our ability to recruit and retain effective sales, marketing and customer service personnel;

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our ability to obtain and retain access to physicians or persuade adequate numbers of physicians to prescribe VTAMA and any future products;

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the inability to manufacture and to price VTAMA and any future products at a price point sufficient to ensure an adequate and attractive level of profitability;

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the extent to which coverage and adequate reimbursement for VTAMA and any future products will be available from government health administration authorities, private health insurers and other organizations;

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the risks associated with potential co-promotion or partnership agreements, including the failure to realize the expected benefits of such arrangements; and

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other unforeseen costs, expenses and risks associated with the commercialization of biopharmaceutical products, including compliance costs.

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our ability to successfully implement and execute on a marketing strategy for VTAMA and to commercialize any of our product candidates in the United States and internationally, if approved, whether alone or in collaboration with others;

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acceptance by physicians, payers, and patients of the benefits, safety, and efficacy of VTAMA or any product candidates, if approved, including relative to alternative and competing treatments;

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timely completion of our nonclinical studies and clinical trials, which may be significantly slower or cost more than we currently anticipate and will depend substantially upon the performance of third-party contractors;

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whether we are required by the FDA or similar foreign regulatory authorities to conduct additional clinical trials or other studies beyond those planned to support the approval and commercialization of our product candidates or any future product candidates;

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acceptance of our proposed indications and primary and secondary endpoint assessments relating to the proposed indications of our product candidates by the FDA and similar foreign regulatory authorities;

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the prevalence, duration, and severity of potential side effects or other safety issues experienced with VTAMA or our product candidates;

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the timely receipt of necessary marketing approvals from the FDA and similar foreign regulatory authorities;

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achieving, maintaining, and, where applicable, ensuring that our third-party contractors achieve and maintain, compliance with our contractual obligations and with all regulatory requirements applicable to VTAMA or any of our product candidates;

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the willingness of physicians and patients to utilize or adopt VTAMA and our product candidates, if approved;

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the ability of third parties upon which we rely to manufacture clinical trial and commercial supplies of VTAMA or any of our product candidates to remain in good standing with relevant regulatory authorities and to develop, validate, and maintain commercially viable manufacturing processes that are compliant with Current Good Manufacturing Practice (“cGMP”);

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the availability of coverage and adequate reimbursement from private third-party payers and governmental healthcare programs, such as Medicare and Medicaid;

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patient demand for any approved products;

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our ability to establish and enforce intellectual property rights in and to any current and future products and product candidates;

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our ability to avoid third-party patent interference, intellectual property challenges, or intellectual property infringement claims; and

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the ability to raise any additional required capital on acceptable terms, or at all.

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disrupting the supply chain and the manufacture or shipment of drug substances and finished drug products for our product candidates for use in our research, preclinical studies and clinical trials;

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delaying, limiting or preventing our employees and CROs from continuing research and development activities;

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impeding our clinical trial initiation and recruitment and the ability of patients to continue in clinical trials, including the risk that participants enrolled in our clinical trials will contract COVID-19 while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events;

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impeding testing, monitoring, study procedures (such as endoscopies that are deemed non-essential), data collection and analysis and other related activities that may impact the integrity of subject data and clinical study endpoints; and

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affecting the business of the FDA, European Medicines Agency (“EMA”) or other regulatory authorities, which could result in delays in meetings related to ongoing or planned clinical trials.

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failure to obtain regulatory authorization to commence a clinical trial or reaching consensus with regulatory authorities regarding the design or implementation of our studies;

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other regulatory issues, including the receipt of any inspectional observations on FDA’s Form-483, Warning or Untitled Letters, clinical holds, or complete response letters or similar communications/objections by other regulatory authorities;

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unforeseen safety issues, or subjects experiencing severe or unexpected adverse events;

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occurrence of serious adverse events in trials of the same class of agents conducted by other sponsors;

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lack of effectiveness during clinical trials;

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resolving any dosing issues, including those raised by the FDA or other regulatory authorities;

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inability to reach agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;

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slower than expected rates of patient recruitment or failure to recruit suitable patients to participate in a trial;

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failure to add a sufficient number of clinical trial sites;

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unanticipated impact from changes in or modifications to protocols or clinical trial design, including those that may be required by the FDA or other regulatory authorities;

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inability or unwillingness of clinical investigators or study participants to follow our clinical and other applicable protocols or applicable regulatory requirements;

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an IRB or EC refusing to approve, suspending, or terminating the trial at an investigational site, precluding enrollment of additional subjects, or withdrawing their approval of the trial;

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premature discontinuation of study participants from clinical trials or missing data;

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failure to manufacture or release sufficient quantities of our product candidates or failure to obtain sufficient quantities of active comparator medications for our clinical trials, if applicable, that in each case meet our quality standards, for use in clinical trials;

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inability to monitor patients adequately during or after treatment; or

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inappropriate unblinding of trial results.