What changed in this filing

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Item 1. Business

2025-03-31 compared with 2024-03-20 · 206 added, 133 removed, 625 unchanged (35% of the section changed)

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Our technology comprises a drug-agnostic oral delivery platform, the RaniPill capsule, which is designed to deliver a wide variety of drug substances, including antibodies, proteins, peptides, and oligonucleotides.

We are currently developing two configurations of the platform – the RaniPill GO and the RaniPill HC.

We have two configurations of the platform – the RaniPill GO and the RaniPill HC.

The RaniPill GO is designed to deliver up to a 3 mg dose of drug in microtablet form with high bioavailability.

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We have tested preclinically the RaniPill HC with multiple therapeutics, including antibodies and a peptide.

We intend to initiate clinical testing of the RaniPill HC in the second half of 2024.

We believe that, together, the RaniPill GO and RaniPill HC could enable us to deliver most biologics currently on the market with convenient, oral dosing.

We intend to initiate clinical testing of the RaniPill HC in mid-2025.

We believe the RaniPill capsule technology could enable us to deliver most biologics currently on the market with convenient, oral dosing.

Data Overview

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In our clinical studies, our product candidates were generally well tolerated and no serious adverse events were observed.

Preclinically, we have tested 15 molecules in the RaniPill capsule, including eight antibodies, six peptides and one large protein.

Preclinically, we have tested 19 molecules in the RaniPill capsule, including ten antibodies, seven peptides, one Fc-fusion protein and one large protein.

We have conducted preclinical testing of more than 7,000 RaniPill capsules in vivo and in vitro.

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The RaniPill capsule was well tolerated with no treatment-related adverse events and all animals remained clinically healthy throughout the study.

As of January 1, 2024, we had tested more than 200 RaniPill HC devices in vivo including delivery of a peptide and multiple different antibodies.

The RaniPill HC represents a significant opportunity to potentially enable the oral delivery of more than ninety additional biologics currently on the market, including therapeutics like dupilumab, secukinumab, pembrolizumab, etanercept and trastuzumab.

We intend for the RaniPill HC to be ready for potential Phase 1 clinical trials in the second half of 2024.

As of January 1, 2025, we had tested more than 350 RaniPill HC devices in vivo including delivery of multiple different antibodies and peptides.

We intend to initiate clinical testing of the RaniPill HC in mid-2025.

Business Update

In November 2023, we announced a strategic program prioritization, expansion of manufacturing and plans to streamline business operations to support near-term value drivers and long-term growth of the RaniPill technology platform (the “Restructuring”).

The plans include strategic prioritization of its key development programs, RT-102, RT-111 and the RaniPill HC and expansion of our manufacturing footprint to support increased scale and partnerships, and cost reduction initiatives that align with our near-term goals, including a reduction in our workforce by approximately 25%.

As part of the strategic focusing of the business, we have paused work on our RT-105 and RT-110 programs and we terminated our RT-101 program, which was the RaniPill capsule containing octreotide.

Collaboration

In June 2024, we entered into a Collaboration Agreement (the “ProGen Collaboration Agreement”) with ProGen Co., Ltd.

Under the ProGen Collaboration Agreement, the parties will collaborate to manufacture, develop, seek regulatory approvals for and, if approved, commercialize a product (RT-114) combining ProGen’s GLP-1/GLP-2 dual agonist compound, PG-102, and the RaniPill HC oral delivery device (the “Device”) in the field of weight management (including without limitation obesity, weight reduction and weight maintenance) in humans (the “ProGen Collaboration”).

Under the ProGen Collaboration Agreement, development costs, as well as operating profits and losses from the commercialization of the Product, will be equally shared by us and ProGen.

We and ProGen each granted to the other party an exclusive right and license (except with respect to the other party’s affiliates and sublicensees) to certain intellectual property to develop RT-114 for weight management and an exclusive right and license to seek regulatory approval for, and to use, sell, offer to sell, import and commercialize RT-114 in their assigned territories.

The parties share responsibility for the development of RT-114 worldwide, with Rani leading such development for preclinical activities through Phase 1 clinical trials.

After initiation of the first Phase 2 clinical trial, we will lead development and commercialization of RT-114 in the United States, Canada, Europe (including the United Kingdom) and Australia, and ProGen will lead development and commercialization in all other countries.

See “License and Evaluation Agreements – ProGen Co., Ltd.” below.

In October 2024, we entered into a securities purchase agreement (the “October Securities Purchase Agreement”) with an institutional investor relating to the issuance and sale of:

(i) 3,000,000 shares of our Class A common stock, (ii) pre-funded warrants to purchase 333,333 shares of Class A common stock, and (iii) Series C common warrants, which accompany the Class A common stock and pre-funded warrants, to purchase an aggregate of 3,333,333 shares of Class A common stock (the “October Offering”).

The aggregate net proceeds from the October Offering totaled $9.4 million, after deducting placement agent fees and other offering expenses payable by us, and excluding potential proceeds, if any, from the exercise of the pre-funded warrants and Series C common warrants issued in the October Offering.

In October 2024, the pre-funded warrants were fully exercised for de minimis proceeds.

In July 2024, we entered into a securities purchase agreement (the “July Securities Purchase Agreement”) with an institutional investor relating to the issuance and sale of:

(i) 2,800,000 shares of its Class A common stock, (ii) pre-funded warrants to purchase 446,753 shares of Class A common stock, (iii) Series A common warrants, which accompany the Class A common stock and pre-funded warrants, to purchase an aggregate of 3,246,753 shares of Class A common stock (the “Series A Warrants”) and (iv) Series B common warrants, which accompany the Class A common stock and pre-funded warrants, to purchase an aggregate of 3,246,753 shares of Class A common stock (the “July Offering”).

Pursuant to the October Securities Purchase Agreement, the Series A Warrants from the July Offering were cancelled.

The aggregate net proceeds from the July Offering totaled $8.9 million, after deducting placement agent fees and other offering expenses, and excluding potential proceeds, if any, from the exercise of the Series B common warrants issued in the July Offering.

In August 2024, the pre-funded warrants were fully exercised for de minimis proceeds.

Preclinical Data

In March 2025, we announced preclinical data demonstrating bioequivalence of RT-114, a GLP-1/GLP-2 dual agonist (PG-102) delivered orally via the RaniPill capsule, to subcutaneously administered PG-102.

RT-114 yielded a relative bioavailability of 111% compared to PG-102 delivered subcutaneously with comparable pharmacokinetic profiles and weight loss.

RT-114 was well tolerated and was excreted without sequelae in all subjects.

For information regarding the preclinical study and the RT-114 program, see the section titled “Our Pipeline Programs - RT-114:

GLP-1/GLP-2 dual agonist for the treatment of obesity” for more information.

In February 2025, we announced preclinical data demonstrating successful oral delivery of the glucagon-like peptide-1 receptor (“GLP-1”) agonist semaglutide via the RaniPill HC (“RT-116”).

In the study, RT-116 demonstrated comparable bioavailability, pharmacokinetics and weight loss to subcutaneous (“SC”) administration of semaglutide.

Further, RT-116 was well tolerated with no serious adverse events.

In October 2024, we announced new pharmacokinetic data from a preclinical study evaluating a GLP-1, GIP and glucagon receptors incretin triagonist with a delivery method mimicking the RaniPill route of administration.

The preclinical study evaluated the pharmacokinetic (“PK”) and pharmacodynamic (“PD”) profiles of an incretin triagonist (GLP-1, GIP, glucagon

receptors) when delivered via an endoscope-guided transenteric administration to mimic the RaniPill route of administration, versus the traditional administration route of subcutaneous injection.

The study was conducted in canines separated into two groups.

In Group 1 (N=3), 0.12 mg/kg of drug was administered via transenteric delivery by endoscope.

In Group 2 (N=5), 0.12 mg/kg of drug was administered by SC injection.

Blood samples were collected over 2 weeks for analysis of serum drug concentrations and various PD and safety biomarkers.

A single dose of drug delivered via either transenteric or SC routes elicited rapid decreases in body weight and serum lipids.

Weight loss observed following transenteric delivery was 9.7 ± 2.5 % versus 6.9 ± 2.1 % following SC injection and is believed to be due to early satiety leading to reduced caloric intake.

Additionally, the bioavailability of drug delivered via the transenteric route was comparable to that of drug delivered via the SC route at the same dose.

The drug was well tolerated in both groups with no serious adverse events (SAEs) observed or changes in safety markers examined.

Transenteric delivery yielded 80% relative bioavailability versus SC and differences between PK parameters (AUC, C max , T max ) were not statistically significant.

CEO Compensation

In November 2023, the Company’s Board of Directors (“Board”) approved a reduction in the annual salary of Talat Imran, the Company’s Chief Executive Officer, from $520,000 to $100,000, effective November 1, 2023 through December 31, 2024 or until such time as the Company receives gross proceeds of $50,000,000 or more, in the aggregate, from equity financing and/or one or more non-dilutive strategic, licensing or partnering transactions (the “Financing Threshold”).

In November 2024, the Board approved to extend the reduction in annual salary of Talat Imran through December 31, 2025 or until the Financing Threshold is met.

Pipeline Overview

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We believe selection of these targets will allow us to potentially accelerate product approval and market launch, while also broadening patient, provider, and payor acceptance of the RaniPill capsule.

In addition, we intend to enter into licenses and collaborations with biopharmaceutical companies for the use of our oral delivery technology to develop and commercialize oral versions of their biologics and drugs.

Below is a summary of our product candidate pipeline.

We envision complementing these programs with robust partnering activities to maximize the value inherent in the RaniPill capsule.

RT-XXX refers to the RaniPill capsule containing a biologic or drug.

* Clinical timelines are subject to potential regulatory agency review delays.

** Partnered with Celltrion, Inc.

Celltrion, Inc.

supplies the drug pursuant to a license and supply agreement and has a right of first negotiation for development and commercial rights following completion of a Phase 1 clinical trial that meets its primary endpoint(s).

** RT-114 is the subject of a worldwide collaboration with ProGen Co.

***Ustekinumab and adalimumab biosimilars are supplied by Celltrion.

Celltrion grants us a license and drug supply for each drug.

Our Pipeline Programs

GLP-1/GLP-2 dual agonist for the treatment of obesity

Market overview

The Centers for Disease Control and Prevention estimates that more than 2 in 5 adults (age 20 and over) in the U.S.

have obesity based on data from 2017 to March 2020, which is more than 100 million people in the U.S.

The global market for anti-obesity treatments is estimated to reach $100 billion by 2030.

Several anti-obesity treatments are currently available, including GLP-1 agonist semaglutide (marketed as Wegovy® by Novo Nordisk A/S) and GLP-1/gastric inhibitory polypeptide (GIP) tirzepatide (marketed as

Zepbound® by Eli Lilly & Co.).

Many potential treatments are in development for obesity and weight management.

A real-world study by Blue Health Intelligence found that more than 30% of GLP-1 users discontinue treatment within the first month of use and less than half of those prescribed stay on the medication for 12 weeks or more.

Our solution:

We are developing RT-114, a RaniPill capsule containing a GLP-1/GLP-2 dual agonist, for the treatment of obesity.

We believe RT-114 may be differentiated from other obesity treatments with regards to tolerability and better preservation of lean mass.

In addition, pharmacokinetic / pharmacodynamic data of the drug substance (“DS”) in RT-114 support potential dosing of oral RT-114 on a weekly schedule, which may improve patient compliance.

We are targeting a profile for RT-114 of once a week oral dosing, potential for better tolerability with more frequent, smaller doses than injectables, potential for less frequent administration than oral competitors and less API required compared to chemistry-based oral molecules.

We are conducting preclinical studies with RT-114.

RT-114 is the subject of a collaboration between ProGen and us.

The drug substance used in RT-114 is a GLP-1/GLP-2 dual agonist known as PG-102 developed by ProGen.

In March 2025, we announced preclinical data demonstrating bioequivalence of RT-114, PG-102 delivered orally via the RaniPill capsule, to subcutaneously administered PG-102.

RT-114 yielded a relative bioavailability of 111% compared to PG-102 delivered subcutaneously with comparable pharmacokinetic profiles.

RT-114 was well tolerated with no changes in drug-related safety profile compared to delivery and was excreted without sequelae in all subjects.

Average peak weight loss was the same in both groups with greater variability with subcutaneous dosing (6.7% ± 0.5% for RT-114 and 6.7% ± 2.2% for subcutaneous PG-102).

ProGen’s preclinical studies demonstrated that treatment with PG-102 resulted in greater glycemic control while inducing a similar degree of body weight loss versus semaglutide and tirzepatide.

ProGen presented results from its Phase 1 single-ascending dose study of PG-102 at the 2024 American Diabetes Association conference in which PG-102 showed a favorable safety profile with lower frequencies of gastrointestinal (“GI”) side effects compared to competitors’ trials in similar settings.

In addition, preclinical studies of PG-102 have demonstrated in a diet-induced obesity (DIO) mouse model weight loss and improved body composition (fat versus lean mass loss) under similar weight loss condition compared to dapiglutide and tirzepatide.

Data are shown in ±SEM

HFD=high fat diet.

We intend to initiate a Phase 1 clinical trial of RT-114 in mid-2025.

Ustekinumab for the treatment of inflammatory conditions

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The study evaluated the safety, and tolerability of a single administration of RT-111 in healthy adult volunteers.

Of the 55 participants, 20 orally ingested RT-111 containing a single 0.5 mg dose of ustekinumab biosimilar and 20 orally ingested RT-111 containing a single 0.75 mg dose of ustekinumab biosimilar, while a control group of 15 participants received a single 0.5 mg subcutaneous injection of STELARA, a commercial formulation of ustekinumab for subcutaneous (“SC”) administration.

In the Phase 1 study, RT-111 was generally well tolerated, with no serious adverse events (“SAE”) noted during the study.

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No participants reported difficulty swallowing the capsule and capsule remnants passed from all participants without sequelae.

Pharmacokinetics (“PK”)

Pharmacokinetics

• Oral RT-111 delivered 0.5mg and 0.75mg of ustekinumab biosimilar with high bioavailability (estimated bioavailability of 84% for 0.5mg RT-111 relative to 0.5mg SC STELARA®).

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License and Supply Agreement

In January 2023, we announced entering into a License and Supply Agreement with Celltrion under which we receive a license and supply of Celltrion’s ustekinumab biosimilar for development and commercialization of RT-111 worldwide, subject to a right of first negotiation for Celltrion following completion of a Phase 1 clinical trial that meets its primary endpoint(s).

We believe the Phase 1 clinical trial that we completed with RT-111, the topline data of which we announced in February 2024, satisfies the requirements for triggering Celltrion’s right of first negotiation.

We intend to advance clinical development of RT-111 at higher doses.

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Preclinical pharmacodynamic study

We conducted a 6-week pharmacodynamic study of the RT-102 drug substance PTH (1-34) to evaluate the effect of daily RT-102 drug substance (“DS”) intraperitoneal injections on bone mineral density in a rodent model of osteoporosis.

We conducted a 6-week pharmacodynamic study of the RT-102 drug substance PTH (1-34) to evaluate the effect of daily RT-102 drug substance intraperitoneal injections on bone mineral density in a rodent model of osteoporosis.

The study compared two control groups of rodents undergoing sham surgery (N=10) and ovariectomy (N=10) receiving no drug, to three overiectomized groups each dosed with 5 mcg/kg per day of either RT-102 DS (N=10), teriparatide (N=10), or abaloparatide (N=10).

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No serious adverse events were reported in the study.

We plan to initiate a Phase 2 clinical trial of RT-102 in 2024.

Study Part 1 - Topline Results

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In addition, we obtained guidance from the FDA on our preclinical and clinical development plans for RT-102.

We intend to initiate a Phase 2 clinical trial of RT-102 in 2024.

Anti-TNF-alpha antibody for the treatment of psoriatic arthritis

The next step for this program is to initiate a Phase 2 clinical trial of RT-102.

Anti-TNF-alpha antibody for the treatment of rheumatoid arthritis

Market overview

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Adalimumab, sold by AbbVie Inc.

under the brand name Humira, generated sales of approximately $21.2 billion in 2022.

Adalimumab is approved by the FDA and EMA to treat a range of autoimmune conditions, including psoriasis, rheumatoid arthritis, and Crohn’s disease.

under the brand name Humira, generated U.S.

sales of approximately $7.14 billion in 2024.

Adalimumab is approved by the FDA and EMA to treat a range of autoimmune conditions, including rheumatoid arthritis, psoriasis and Crohn’s disease.

alone, there are an estimated one and one-half million patients with rheumatoid arthritis, seven million with psoriasis, and three million with Crohn’s disease or ulcerative colitis.

At least eight Humira biosimilars entered the U.S.

market over the course of 2023.

At least eight Humira® biosimilars have entered the U.S.

market including Yuflyma®, a high-concentration, citrate-free adalimumab biosimilar marketed by Celltrion.

Patients who use adalimumab administer the drug through a subcutaneous injection once every two weeks.

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Under the Celltrion Agreement for adalimumab, Celltrion will have a right to terminate the agreement if we do not initiate a Phase 1 clinical trial with RT-105, or fail to deliver to Celltrion topline data from a Phase 1 trial that meets its primary endpoint(s), within certain agreed time periods.

We anticipate resuming this program in time to enable us to satisfy these requirements.

PTH for the treatment of hypoparathyroidism

Market overview

Hypoparathyroidism is a rare condition of low levels of serum PTH resulting in low calcium levels in the blood.

The prevalence of hypoparathyroidism in the United States is approximately 115,000 people.

PTH is currently approved for the treatment of hypoparathyroidism by the FDA and EMA.

PTH treatment requires lifelong daily injections but has suboptimal efficacy.

Treatment of hypoparathyroidism is most effective with consistent and sustained plasma levels of PTH.

Our solution:

We are developing RT-110, the RaniPill capsule containing our second novel formulation of PTH, for oral treatment of hypoparathyroidism.

We are creating a sustained release formulation of RT-110 which is intended to provide continuous exposures of the hormone required to normalize the calcium imbalance in hypoparathyroidism patients.

We have worldwide commercial rights to RT-110.

We believe that there is an unmet need for a delivery method more convenient than injection, and we further believe that the RaniPill capsule could provide for a treatment regimen that can better maintain consistent and sustained plasma levels of PTH than the current treatment regimen of daily PTH injections.

In November 2023, we announced the pausing of development of RT-110 as part of a strategic focusing of the business.

The next milestone for this program would be to initiate a Phase 1 clinical trial in healthy volunteers.

The Market and Our Strategy

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The affected population is expected to continue to grow as the population ages.

Chronic conditions, including autoimmune diseases, metabolic disorders, cancers, and cardiovascular diseases are increasingly being treated with biologics.

In 2022, six of the ten highest revenue-producing drugs in the world were biologics.

Chronic conditions, including obesity, autoimmune diseases, metabolic disorders, cancers, and cardiovascular diseases are increasingly being treated with biologics.

In 2023, eight of the ten highest revenue-producing drugs in the world were biologics.

Current treatments using biologics are primarily via injections.

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Biologics include, for example, recombinant therapeutic proteins, peptides, and monoclonal antibodies, as well as cell and gene therapies.

The global biologics market size is estimated to be $429.5 billion in 2024 and is expected to reach $601.26 billion by 2029.

The global biologics market size was calculated to be $511.0 billion in 2024 and is expected to reach $1.4 trillion by 2033.

Biologics must generally be administered through intravenous, intramuscular, or subcutaneous injection.

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Bioavailability refers to the proportion of a delivered dose that reaches the bloodstream in active form.

Attempts at oral delivery of biotherapeutics have remained largely unsuccessful due to the rapid degradation and digestion of biologics in the gastrointestinal (“GI”) environment before they can be absorbed into the bloodstream.

Attempts at oral delivery of biotherapeutics have remained largely unsuccessful due to the rapid degradation and digestion of biologics in the gastrointestinal environment before they can be absorbed into the bloodstream.

Our solution is a novel, proprietary and patented platform technology referred to as the RaniPill capsule, an orally ingestible pill designed to automatically deploy in the small intestine to administer a precise therapeutic dose of a biologic into the intestinal wall.

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We are pursuing a number of clinical and preclinical pipeline programs utilizing our RaniPill capsule.

In addition, our newly designed high-capacity oral biologic delivery device, the RaniPill HC, has the potential to deliver 500%-plus higher payloads than our current RaniPill GO capsule.

We believe this is a significant breakthrough in drug delivery with the potential to provide expansive opportunities for the company, such that we could potentially pursue a convenient dosing option for over 50 additional biologics, for internal development or through partnership, including such biologics as dupilumab, pembrolizumab, etanercept, trastuzumab and secukinumab.

We believe the RaniPill capsule has the potential to deliver more than 90 biologics currently on the market, including such biologics as semaglutide, dupilumab, pembrolizumab, etanercept, trastuzumab and secukinumab.

We believe that oral biologics utilizing our RaniPill technology have the potential to disrupt the large and growing biologics market.

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• Pursue validated and commercially established market opportunities.

We intend to pursue high-value markets with biologics that are already approved or validated where we can develop differentiated products.

We intend to pursue high-value markets with biologics where we can develop differentiated products.

We believe that these products will take market share from available therapies, while also expanding existing markets by reaching new patient populations that otherwise are not being treated by injectable biologics.

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• Invest in RaniPill capsule capabilities.

We intend to become a leader in oral biologics by continuing to invest in our technology, such as by expanding payload capacity and developing novel biologic formulations to maximize the number of therapeutic targets and addressable markets.

We intend to become a leader in oral biologics by continuing to invest in our technology, such as by expanding payload capacity to maximize the number of therapeutic targets and addressable markets.

• Expand our reach by selectively entering into strategic partnerships.

We are actively exploring strategic partnerships to enable us to expand our commercial reach and enable oral administration of a broader array of biologics and drugs.

We are actively exploring partnering of our RaniPill technology with third party biopharmaceutical companies for the oral delivery of their biologics and drugs.

• Continue to strengthen our intellectual property portfolio.

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We are currently developing two configurations of the platform – the RaniPill GO and the RaniPill HC.

The RaniPill GO is designed to deliver up to a 3 mg dose of drug in microtablet form with high bioavailability.We are also developing a high-capacity version of the RaniPill capsule known as the RaniPill HC, which is intended to enable delivery of drug payloads up to 200µL in liquid form with high bioavailability.

We have two configurations of the platform – the RaniPill GO and the RaniPill HC.

The RaniPill GO is designed to deliver up to a 3 mg dose of drug in microtablet form with high bioavailability.

We are also developing a high-capacity version of the RaniPill capsule known as the RaniPill HC, which is intended to enable delivery of drug payloads up to 200µL in liquid form with high bioavailability.

Each of our product candidates is a RaniPill capsule containing a biologic.

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Dissolution of the coating leads to a series of steps that result in a biologic being delivered into the highly vascularized wall of the small intestine so that the biologic can be absorbed into the vasculature and enter the bloodstream.

The following illustrations depict the clinically tested RaniPill GO capsule traversing through and deploying within a lumen of the intestine illustrated in cross section.

The following illustrations depict the RaniPill HC capsule traversing through and deploying within a lumen of the intestine illustrated in cross section.

As the RaniPill capsule exits the stomach and enters the small intestine, the higher pH environment of around 6.5 in the jejunum begins to dissolve the coating.

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Inflation of the balloon orients a microneedle contained within the balloon approximately perpendicular to the intestinal wall.

The pressure in the balloon delivers the microneedle, which is smaller than a grain of rice, into the intestinal wall.

The pressure in the balloon delivers drug through the microneedle, which is smaller than a grain of rice, into the intestinal wall.

The microneedle dissolves in the moist tissue environment, and the drug is absorbed into the vasculature and thereby into the bloodstream.

The balloon immediately deflates upon microneedle delivery and is excreted through normal digestive processes.

The RaniPill HC operates similar to the RaniPill GO except that, instead of delivering a dissolvable microneedle containing a solid microtablet of drug, the RaniPill HC uses a dissolvable needle to deliver the drug payload in liquid form.

The RaniPill GO operates similar to the RaniPill HC except that it delivers a dissolvable microneedle containing a solid microtablet of drug instead of delivering the drug payload in liquid form.

Features and advantages of the RaniPill capsule

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• Protective coating avoids deployment in the stomach – The proprietary protective coating formulation is pH-sensitive, enabling the RaniPill capsule to maintain its integrity through the acidic environment in the stomach for deployment in the small intestine.

• Protection of the drug prior to delivery – The microneedle and drug are protected from intestinal fluid until delivery, and then the rapid injection of the microneedle into the intestinal wall during delivery provides for little or no exposure of the microneedle or drug to intestinal fluid.

This technique serves to overcome the body’s natural mechanisms that break biologics down in the harsh GI environment and thus block biologics from reaching the blood stream from within the intestine.

• Protection of the drug prior to delivery – The microneedle and drug are protected from intestinal fluid until delivery, and then the rapid injection of the microneedle into the intestinal wall and delivery of drug provides for little or no exposure of the microneedle or drug to intestinal fluid.

This technique serves to overcome the body’s natural mechanisms that break down biologics in the harsh GI environment and thus block biologics from reaching the blood stream from within the intestine.

• Delivery in both fed and fasted states – The RaniPill capsule is designed to deliver the drug payload regardless of whether the patient ingests the RaniPill capsule with or without food, which we expect will allow for more flexible dosing regimens and improved patient adherence to a given regimen.

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This allows a single platform design to be used with multiple drugs.

• Optimized dosing regimen – Based on the confirmed patient preference for oral delivery alternatives, we expect better treatment adherence with oral dosing versus injections, thus enabling a more clinically-favorable dosing regimen.

• Optimized dosing regimen – Based on confirmed patient preference for oral delivery alternatives, we expect better treatment adherence with oral dosing versus injections, thus enabling a more clinically-favorable dosing regimen.

For example, the RaniPill capsule may enable a regimen of small, more frequent doses, versus larger less frequent doses for injections, to improve treatment adherence.

In addition, small, more frequent dosing may allow for therapeutic exposures to be maintained within a narrow range, whereas larger less frequent injection dosing can lead to large variations in therapeutic exposure, which may contribute to adverse events, loss of efficacy, and increased propensity for immunogenic response.

We continue to develop the RaniPill HC, a high-capacity RaniPill capsule designed to deliver drug payloads up to 200µL, 500%-plus higher than the payload capacity of the RaniPill GO.

We continue to develop the RaniPill HC, a high-capacity RaniPill capsule designed to deliver drug payloads up to 200µL.

As of January 1, 2025, we had tested more than 350 RaniPill HC devices in vivo including delivery of multiple different antibodies and peptides.

We intend to initiate clinical testing of the RaniPill HC in mid-2025.

In March 2025, we announced preclinical data demonstrating bioequivalence of RT-114, a GLP-1/GLP-2 dual agonist (PG-102) delivered orally via the RaniPill HC, to subcutaneously administered PG-102.

RT-114 yielded a relative bioavailability of 111% compared to PG-102 delivered subcutaneously with comparable pharmacokinetic profiles and weight loss.

The RaniPill capsule was well tolerated with no changes in drug-related safety profile compared to subcutaneous delivery and was excreted without sequelae in all canines.

RT-114 achieved a 90% delivery success rate (9 out of 10 canines).

For information regarding the preclinical study and the RT-114 program, see the section titled “Our Pipeline Programs - RT-114:

GLP-1/GLP-2 dual agonist for the treatment of obesity” for more information.”

Semaglutide Study

In February 2025, we announced results from a nonclinical pharmacokinetic and pharmacodynamic study of the GLP-1 agonist semaglutide administered via the RaniPill HC.

The nonclinical pharmacokinetic and pharmacodynamic study was conducted to examine the effects of semaglutide delivered orally via the RaniPill (RT-116) versus a subcutaneous injection comparator group.

The 2x2 crossover study was conducted in two parts with a period of four weeks separating the two groups to evaluate the PK, PD and safety of RT-116.

Eight canines were randomized into two groups who received 0.5mg of semaglutide delivered via oral administration of the RaniPill HC (N=4) or subcutaneous injection (N=4).

Endpoints included plasma drug concentrations, body weight, food intake, lipid profile, and safety.

Data Highlights

Semaglutide was successfully delivered in 7 of 8 canines that received the RaniPill capsule.

Semaglutide administered via the RaniPill capsule was well tolerated with no serious adverse events.

Cmax, Tmax, and AUC were comparable for semglutide administered via RaniPill capsule and subcutaneous administration of semaglutide.

Oral administration via the RaniPill capsule demonstrated bioavailability and biological activity comparable to subcutaneous administration.

The relative bioavailability of oral semaglutide was 107% versus subcutaneous administration.

Both groups saw comparable weight loss which appeared to be driven by decreased food intake that coincided with rises in plasma drug levels thus indicating there is a PD effect to treatment.

Both groups saw comparable moderate decreases in serum triglycerides and cholesterol.

Previous Studies

In September 2023, we announced three positive preclinical studies which support the development of the RaniPill HC device.

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• The RaniPill HC containing Fe57 showed a positive drug signal comparable to subcutaneous injection.

In October and November 2023, we announced the completion of two preclinical studies of the RaniPill HC with antibodies, adalimumab and an undisclosed anti-interleukin antibody (“Undisclosed MAB”).

In October and November 2023, we announced the completion of two preclinical studies of the RaniPill HC with antibodies, adalimumab and dupilumab.

In the two studies, the RaniPill HC achieved an oral delivery success rate of 100% (10/10).

In one study, we tracked the serum concentrations of adalimumab, following the oral administration of the enteric-coated RaniPill HC capsule containing 11mg of Humira (adalimumab) to four canine models.

In the second study, we tracked the serum concentrations of the Undisclosed MAB, following the oral administration of the enteric-coated RaniPill HC capsule containing 16.5mg of Undisclosed MAB to six canine models.

In the second study, we tracked the serum concentrations of

dupilumab, following the oral administration of the enteric-coated RaniPill HC capsule containing 16.5mg of dupilumab to six canine models.

In both studies, the RaniPill HC was well tolerated, all animals remained healthy throughout the study period with no clinical findings or adverse events, and all device remnants were excreted normally without sequelae.

Comparing the pharmacokinetic results of 11mg of adalimumab delivered via the RaniPill HC (N=4) with historical pharmacokinetic data we generated with 5mg of an adalimumab biosimilar (GP2017) delivered via subcutaneous injection (N=3), there is a higher estimated bioavailability of adalimumab delivered via the RaniPill HC relative to the subcutaneous injection route.

Adalimumab 11mg via RaniPill HC vs Adalimumab Biosimilar 5mg via Subcutaneous Injection

Pharmacokinetics of Adalimumab (11mg) Delivered Orally via RaniPill HC Capsules to Awake Canines (N=4)

All Data are Means ± SE

Pharmacokinetics of Undisclosed MAB (16.5mg) Delivered Orally via RaniPill HC Capsules to Awake Canines (N=6)

Pharmacokinetics of Dupilumab (16.5mg) Delivered Orally via RaniPill HC Capsules to Awake Canines (N=6)

All Data are Means ± SE

Preliminary preclinical testing supports the potential for RaniPill HC to have high reliability, and initial analysis of drug delivery via the RaniPill HC shows a potential for mimicking parenteral (subcutaneous) administration.

We intend for the RaniPill HC to be ready for potential Phase 1 clinical trials in the second half of 2024.

60-Day GLP Study

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The RaniPill platform, if marketed without a biologic, would be classified by the FDA as a device regulated by the Center for Devices and Radiological Health (“CDRH”).

A biologic, if marketed without the RaniPill platform, would be classified by the FDA as either a “biological product” regulated by the Center for Biologics Evaluation and Research (“CBER”) or a “drug” regulated by the Center for Drug Evaluation and Research (“CDER”).

A biologic, if marketed without the RaniPill platform, would be classified by the FDA as either a “biological product” or a “drug.” Drugs and certain biological products, including monoclonal antibodies and proteins intended for therapeutic use, are regulated by the Center for Drug Evaluation and Research (“CDER”) and certain biological products, including vaccines, cellular products and gene therapy products, are regulated by the Center for Biologics Evaluation and Research (“CBER”).

The classification as biological product or drug would depend on the FDA’s definition of “biological product” with respect to the active ingredient of a product candidate at the time a request for regulatory license or approval is submitted to the FDA to market that product candidate.

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OCP is also responsible for developing guidance and regulations to clarify the regulation of combination products, and for assignment of the FDA center that has primary jurisdiction for review of combination products where the jurisdiction is unclear or in dispute.

It is expected that most of our product candidates will include a biologic within the FDA’s definition of “biological product” and some of our product candidates may include a biologic that will be considered a “drug.” CDER is the lead center for review of therapeutic proteins at this time, thus most of our product candidates will have CDER as the lead center.

It is expected that most of our product candidates will include a biologic within the FDA’s definition of “biological product” and some of our product candidates may include a biologic that will be considered a “drug.” CDER is the lead center for review of monoclonal antibodies and therapeutic proteins at this time, thus most of our product candidates will have CDER as the lead center.

For each product candidate, we will perform numerous preclinical laboratory tests and animal studies, as well as perform human clinical trials.

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License and Evaluation Agreements

ProGen Co., Ltd.

In June 2024, we entered into the ProGen Collaboration Agreement with ProGen.

Under the ProGen Collaboration Agreement, the parties will collaborate to manufacture, develop, seek regulatory approvals for and, if approved, commercialize a product (RT-114) combining ProGen’s GLP-1/GLP-2 dual agonist compound, PG-102, and the RaniPill HC oral delivery device in the field of weight management (including without limitation obesity, weight reduction and weight maintenance) in humans.

Under the ProGen Collaboration Agreement, development costs, as well as operating profits and losses from the commercialization of the Product, will be equally shared by us and ProGen.

The parties share responsibility for the development of RT-114 worldwide, with Rani leading such development for preclinical activities through Phase 1 clinical trials.

Each party has the right to opt-out of the ProGen Collaboration (“Opt-Out”) at any time upon prior written notice to the other party.

Following an Opt-Out, the continuing party shall have sole right to develop, conduct regulatory activities for and commercialize RT-114 on a worldwide basis.

The Opt-Out party shall share all development costs and operating profit (or loss) through the effective date of the Opt-Out, and all costs to complete the conduct of any clinical trials of RT-114 that have been initiated prior to delivery of the Opt-Out notice, even if the costs are incurred or the trials are completed after the effective date of the Opt-Out.

The continuing party shall pay to the Opt-Out party low single to mid-single digit royalties on net sales of RT-114 made after the Opt-Out date depending on when the Opt-Out occurs.

Celltrion license and supply agreements

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In the event Celltrion does not timely exercise the ROFN or Celltrion notifies us that it does not intend to exercise the ROFN or, after timely exercising the ROFN, notifies us that Celltrion withdraws its exercise of the ROFN, or the parties fail to enter into a definitive agreement for the development and commercialization of the applicable program within the exclusive negotiation period, then the ROFN regarding that program will terminate and we will have no further obligations under the Celltrion Agreements related to a ROFN for that program.

The ROFN with respect to RT-111 has expired.

The Celltrion Agreements allocate rights between the parties with respect to inventions generated in performance of the agreement for the manufacture, development and commercialization of each of RT-111 and RT-105, respectively.

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We have a right to terminate each agreement for convenience subject to certain notice periods.

Celltrion has a right to terminate each agreement if we do not achieve certain development milestones with respect to that agreement, and each party has certain rights to terminate the applicable agreement for material breach or safety concerns regarding the stekinumab biosimilar or RT-111, or adalimumab biosimilar or RT-105, respectively.

Novartis evaluation agreement

In May 2015, we entered into an Evaluation and First Rights Agreement (the “Novartis Agreement”) with Novartis Pharmaceuticals Corporation (“Novartis”), in which we agreed to perform certain specified research for Novartis to evaluate two specified Novartis compounds with our oral drug delivery technology.

In August 2019 and July 2020, we amended the agreement to focus on one compound.

Under the agreement, we granted Novartis an exclusive, fully paid-up license to the intellectual property it generates for the sole purpose of delivering that compound via any delivery route other than through use of any microtablet.

Novartis will own intellectual property generated related to that compound and we will own all other intellectual property regardless of inventorship.

We are currently in the process of completing our own internal testing of higher capacity payloads in the RaniPill capsule.

Certain data from such testing was shared with Novartis pursuant to the July 2020 amendment.

Following delivery of a report by us, Novartis will have a right of first negotiation to obtain rights to research, develop, manufacture, and commercialize a specified class of biologics formulated with our delivery technology (“Novartis Field”) for a period of four months.

If we and Novartis do not reach an agreement in this period, for a period of another six months Novartis will have the opportunity to make a topping bid on any third-party transaction proposal in the Novartis Field.

Unless earlier terminated, the Novartis Agreement will expire upon the expiration of the last-to-expire time periods for which Novartis has a right of first negotiation or a right to make a topping bid.

Prior to these periods, Novartis may terminate the Novartis Agreement at any time for convenience, and we and Novartis may terminate the Novartis Agreement for the other party’s uncured material breach.

Novartis has paid us an aggregate of $7.0 million under the Novartis Agreement as of December 31, 2022 and made an equity investment of approximately $5 million in our Series C preferred unit financing.

As part of the organizational transactions in connection with our initial public offering, the Series C preferred units were exchanged for 404,638 Paired Interests.

We did not receive any payments from Novartis under the Novartis Agreement in 2023 and we do not expect any future payments under the Novartis Agreement unless we and Novartis negotiate a new agreement constructed around a higher-capacity payload system.

Celltrion has a right to terminate each agreement if we do not achieve certain development milestones with respect to that agreement, and each party has certain rights to terminate the applicable agreement for material breach or safety concerns regarding the ustekinumab biosimilar or RT-111, or adalimumab biosimilar or RT-105, respectively.

Evaluation agreement

In August 2024, we entered into a contract to conduct evaluation services of certain customer compounds for oral delivery using the RaniPill HC.

This customer paid us an up-front payment of $0.6 million upon execution of the contract.

Upon completion of the evaluation services, we are entitled to a final $0.6 million payment for an aggregate total of $1.2 million due under the contract.

In addition, if agreed upon, the agreement allows for joint filing of certain intellectual property protection in which all associated expenses will be shared equally.

The customer has the ability to terminate the agreement at any time by providing 10 days’ written notice after the effective date of the contract.

The contract can be terminated for cause by either party based on uncured material breach by the other party.

Upon early termination, all ongoing activities under the agreement and all mutual collaboration, development and commercialization licenses and sublicenses will terminate.

Manufacturing and Quality Assurance

We currently manufacture and assemble RaniPill capsules at our facility in San Jose, California.

We also inspect, package and ship finished products to support our clinical trials from this facility.

We currently manufacture and assemble RaniPill capsules ourselves.

We also inspect, package and ship finished products to support our clinical trials.

We are intentionally pursuing a vertically integrated manufacturing strategy, which we believe offers significant advantages, including rapid product iteration, control over our product quality, and the ability to rapidly scale our manufacturing capacity.

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In the case of ustekinumab for RT-111 and adalimumab for RT-105, we obtain supply of drug substance from Celltrion under the Celltrion Agreements.

In the case of PG-102 for RT-114, we obtain supply of drug substance from ProGen under the ProGen Collaboration Agreement.

For other APIs or drug substances, we rely on non-exclusive, third-party relationships with several manufacturers for the drug API or drug substance.

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Development of our product candidates includes identifying sources that can provide consistent quality and increasing quantities of APIs or drug substance to meet our needs through in vitro studies, preclinical studies, and clinical trials, and later into commercialization.

We currently do not have agreements in place for long-term supplies of any API or drug substance, other than ustekinumab biosimilar for RT-111 and adalimumab biosimilar for RT-105.

We currently do not have agreements in place for long-term supplies of any API or drug substance, other than ustekinumab biosimilar for RT-111, adalimumab biosimilar for RT-105 and PG-102 for RT-114.

Availability of API or drug substance supply may inform our decisions regarding which product candidates present the best development opportunities.

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Key competitive factors affecting the commercial success of product candidates we may develop are likely to be efficacy, safety and tolerability profile, reliability, convenience of administration, price, and reimbursement.

Broadly speaking, we will face competition from current and future (generic or biosimilar) manufacturers of the branded injectable versions of our pipeline drugs, manufacturers such as AbbVie Inc., Eli Lilly and Company, Janssen Biotech, Inc., etc.

However, we believe that oral biologics have the potential to take significant market share from current injectable therapies.

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We are aware of certain other companies that are pursuing oral biologics through either device-based or chemistry-based technologies.

We may also face competition from companies that develop oral small molecule therapeutics to the same biological targets as biologics.

We may also face competition from companies that develop oral small molecule therapeutics to the same biological targets as biologics incorporated into our RaniPill capsule.

Early-stage device-based technologies such as the SOMA and LUMI from the Novo Nordisk-MIT collaboration were reported to be in early clinical and preclinical stages, respectively.

Two other companies pursuing a device-based approach are Biograil ApS and Biora Therapeutics, Inc., both of which were reported to be in a preclinical stage of development.

Chemistry-based oral delivery companies include Oramed Pharmaceuticals, Inc., Entera Bio Ltd., Protagonist Therapeutics, Inc., i2O Therapeutics, Intract Pharma, and two with recently approved oral peptide products – Mycappssa from Chiesi Farmaceutici SpA and Rybelsus from Novo Nordisk A/S.

In December 2024, Biora announced that it is undertaking a Chapter 11 sale process.

Chemistry-based oral delivery companies include, but are not limited to, Oramed Pharmaceuticals, Inc., Entera Bio Ltd., Protagonist Therapeutics, Inc., i2O Therapeutics, Intract Pharma, and two with recently approved oral peptide products – Mycapssa from Chiesi Farmaceutici SpA and Rybelsus from Novo Nordisk A/S.

Chemistry-based approaches have limited applications because they work only for small peptides and, even then, with low (often less than 1%) bioavailability, far lower than injections.

In contrast, our versatile technology is designed to deliver biologics, from small peptides to large proteins, irrespective of molecular mass and with bioavailability similar to that of injections.

We also face competition from gene and cell therapy companies.

Further, our product candidates aim to treat chronic diseases.

We could also face competition from implantable device companies, such as Vivani Medical Inc., and gene and cell therapy companies.

Our product candidates aim to treat chronic diseases.

As a result, we also compete with curative therapies on the basis that they cure the chronic disease we are intending to treat.

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Such assessments could cause significant expenditures.

We may be able to reduce expenditures related to these assessments by our strategy of using biologics already approved for marketing.

We may be able to reduce expenditures related to these assessments for biologics already approved for marketing.

Intellectual Property

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This patent family claims many device aspects of the RaniPill platform, including aspects of the RaniPill GO and certain aspects of the RaniPill HC, and the delivery of a wide variety of biologics using the RaniPill platform.

Granted patents and pending patent applications in this core family number more than 270.

As of January 1, 2024, this patent family included 79 patents issued in the United States and 144 patents issued in other jurisdictions (in Australia, Austria, Belgium, Canada, China, Denmark, Finland, France, Germany, India, Ireland, Italy, Japan, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, Turkey, and the United Kingdom), with applications pending in the United States, Australia, Canada, China, Europe, Hong Kong, India, and Japan.

As of January 1, 2025, this patent family included patents issued in the United States and patents issued in other jurisdictions (in Australia, Austria, Belgium, Canada, China, Denmark, Finland, France, Germany, India, Ireland, Italy, Japan, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, Turkey, and the United Kingdom), with applications pending in the United States, Australia, Canada, China, Europe, Hong Kong, and Japan.

We also own several patent families directed to the RaniPill HC.

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This patent family has a priority date in 2014, includes several dozen granted patents and pending patent applications, and is expected to have patent terms extending into at least 2035 if all fees are paid.

As of January 1, 2024, this patent family included 12 patents issued in the United States, 11 patents issued in other jurisdictions (i.e., Australia, Canada, China and Japan), with applications pending in the United States, Australia, Canada, China, Europe, India, and Japan.

We own numerous additional patents and patent applications, with claims to additional biologics, pharmacologic properties of various biologics and various next generation devices, with applications pending in the United States, Australia, Brazil, Canada, China, Europe, Hong Kong, India, Japan, Mexico, and South Korea.

Patents in these families are expected to expire between the late 2030s and early 2040s if all fees are paid.

As of January 1, 2025, this patent family included patents issued in the United States and other jurisdictions (i.e., Australia, Canada, China, India and Japan), with applications pending in the United States, Australia, Canada, China, Europe, and Japan.

We own numerous additional patents and patent applications, with claims to additional biologics, pharmacologic properties of various biologics and other ingestible device technologies, with applications pending in the United States, Australia, Brazil, Canada, China, Europe, Hong Kong, India, Japan, Mexico, and South Korea.

Patents in these families are expected to expire between the late 2030s and mid 2040s if all fees are paid.

Trade secrets and other proprietary information

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The FDA and the sponsor must reach agreement on the PSP.

A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from nonclinical studies, early phase clinical trials, and/or other clinical development programs.

A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric

plan need to be considered based on data collected from nonclinical studies, early phase clinical trials, and/or other clinical development programs.

The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of data or full or partial waivers.

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We are responsible for the selection and monitoring of qualified contract manufacturers, laboratories, and packagers, and, in certain circumstances, qualified suppliers to them.

These facilities and, where applicable, their suppliers are subject to inspections by the FDA at any time, and the discovery of violative conditions, including failure to conform to cGMP, could result in enforcement actions that interrupt the operation of any such facilities or the ability to distribute products manufactured, processed, or tested by them.

These facilities and, where applicable, their suppliers are subject to inspections by the FDA at any time,

and the discovery of violative conditions, including failure to conform to cGMP, could result in enforcement actions that interrupt the operation of any such facilities or the ability to distribute products manufactured, processed, or tested by them.

Accordingly, we must continue to expend time, money, and effort on quality control for our own facilities and the facilities of others which contribute to the commercialization of our final product, to maintain compliance with cGMP and other aspects of regulatory compliance.

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An applicant submitting an ANDA must, for each patent listed against the approved drug in the Orange Book, either (i) state that the ANDA applicant is not seeking approval for a patented method of use, (ii) ask the FDA to delay approval until that patent is expired (a “Paragraph III” certification), or (iii) attest that the patent is invalid, unenforceable, or will not be infringed by the generic product (a “Paragraph IV” certification), which can trigger ANDA litigation over the associated patent.

The purple book contains information about all FDA-licensed biological products regulated by CBER, including licensed biosimilar and interchangeable products and their reference products, and FDA-licensed allergenic, cellular and gene therapy, hematologic, and vaccine products regulated by CBER.

The purple book contains information about all FDA-licensed biological products regulated by CDER, including licensed biosimilar and interchangeable products and their reference products, and FDA-licensed allergenic, cellular and gene therapy, hematologic, and vaccine products regulated by CBER.

The Purple Book includes granted exclusivity information.

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For example, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the “ACA”), which was enacted in March 2010, contains a number of provisions of particular import to the pharmaceutical and biotechnology industries, including, but not limited to, those governing enrollment in federal healthcare programs, a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated, and annual fees based on pharmaceutical companies’ share of sales to federal health care programs.

There have been executive, judicial and Congressional challenges to certain aspects of the ACA.

For example, on June 17, 2021, the United States Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.

Moreover, prior to the U.S.

Supreme Court ruling, on January 28, 2021, President Biden issued an executive order that initiated a special enrollment period coverage through the Affordable Care Act marketplace, and instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare.

Further, on August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (IRA) into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in Affordable Care Act marketplaces through plan year 2025.

There have been executive, judicial and Congressional challenges and amendments to certain aspects of the ACA.

For example, on August 16, 2022, the Inflation Reduction Act of 2022 (“IRA”) was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in Affordable Care Act marketplaces through plan year 2025.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and through a newly established manufacturer discount program.

It is possible that the ACA will be subject to additional challenges in the future.

It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the ACA, or the impact any changes to the ACA may have on our ability to commercialize products or the prices we are able to obtain.

It is unclear how such challenges and the healthcare reform measures of the second Trump administration will impact the ACA, or the impact any changes to the ACA may have on our ability to commercialize products or the prices we are able to obtain.

In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted.

These changes included aggregate reductions to Medicare payments to providers of 2% per fiscal year, which went into effect in April 2013 and, due to subsequent legislative amendments to the statute, including the Infrastructure Investment and Jobs Act, will remain in effect through 2031 unless additional action is taken by Congress.

Further, Congress is considering additional health reform measures.

These changes include aggregate reductions to Medicare payments to providers of 2% per fiscal year pursuant to the Budget Control Act of 2011, which began in April 2013 and, due to subsequent legislative amendments to the statute, including the Infrastructure Investment and Jobs Act, will remain in effect until 2032 unless additional Congressional action is taken.

In addition, recently there has been heightened governmental scrutiny over the manner in which drug manufacturers set prices for their commercial products.

At the federal level, the former Trump administration used several means to propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives.

In July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, the U.S.

Department of Health and Human Services (“HHS”) released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue as well as potential administrative actions HHS can take to advance these principles.

In addition, the IRA, among other things, (i) directs HHS to negotiate the price of certain

single-source drugs and biologics covered under Medicare and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions take effect progressively starting in fiscal year 2023.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.

In response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

It is unclear whether the models will be utilized in any health reform measures in the future.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

At the federal level, the IRA, among other things, (i) directs the U.S.

Department of Health and Human Services (“HHS”) to negotiate the price of certain high-expenditure single-source biologics that have been on the market for at least 11 years covered under Medicare (the “Medicare Drug Price Negotiation Program”) and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions began to take effect progressively starting in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon prices of the first ten drugs that were subject to price negotiations, although the Medicare

Drug Price Negotiation Program is currently subject to legal challenges.

On January 17, 2025, HHS selected fifteen additional products covered under Part D for price negotiation in 2024.

Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.

Further, on December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

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At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

For example, on January 5, 2024, the FDA approved Florida’s Section 804 Importation Program (SIP) proposal to import certain drugs from Canada for specific state healthcare programs.

It is unclear how this program will be implemented, including which drugs will be chosen, and whether it will be subject to legal challenges in the United States or Canada.

Other states have also submitted SIP proposals that are pending review by the FDA.

Any such approved importation plans, when implemented, may result in lower drug prices for products covered by those programs.

Additional health reform measures may continue and affect our business in unknown ways, particularly given the recent change in administration.

The current Trump administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, CMS and related agencies.

These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

These actions may include, for example, directives to reduce agency workforce, rescinding a Biden administration executive order tasking the Center for Medicare and Medicaid Innovation to consider new payment and healthcare models to limit drug spending and eliminating the Biden administration’s executive order that directed HHS to establishing an artificial intelligence (“AI”) task force and developing a strategic plan, and directing certain federal agencies to enforce existing law regarding hospital and price plan transparency and by standardizing prices across hospitals and health plans.

Additionally, in its June 2024 decision in Loper Bright Enterprises v.

Raimondo, the U.S.

Supreme Court overturned the longstanding Chevron doctrine, under which courts were required to give deference to regulatory agencies’ reasonable interpretations of ambiguous federal statutes.

The Loper Bright decision could result in additional legal challenges to current regulations and guidance issued by federal agencies applicable to our operations, including those issued by the FDA.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA.

Data privacy and security obligations

In the ordinary course of our business, we may collect, receive, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, share and store (“process”) proprietary, confidential and sensitive information, including personal data, intellectual property, trade secret, clinical trial data, and proprietary information owned or controlled by ourselves or third parties (collectively, sensitive data).

Our data processing activities may subject us to numerous data privacy and security obligations, including federal, state, local, and foreign laws, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations related to data privacy and security.

Such obligations may include, without limitation, the Federal Trade Commission Act, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act of 2020 (collectively, “CCPA”), other U.S.

state comprehensive privacy laws (such as Virginia, Colorado, Connecticut, and Utah), the European Union’s General Data Protection Regulation 2016/679 (“EU GDPR”) and the United Kingdom’s GDPR (“UK GDPR”).

In the ordinary course of our business, we collect, receive, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, share and store (“process”) proprietary, confidential and sensitive information, including personal data, intellectual property, trade secret, clinical trial data, and proprietary information owned or controlled by ourselves or third parties (collectively, sensitive data).

Our data processing activities subject us to numerous data privacy and security obligations, including federal, state, local, and foreign laws, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations related to data privacy and security.

Such obligations may include, without limitation, the Federal Trade Commission Act, U.S.

state comprehensive privacy laws, the European Union’s General Data Protection Regulation 2016/679 (“EU GDPR”) and the United Kingdom’s GDPR (“UK GDPR”).

Obligations related to the processing of personal data worldwide is rapidly evolving.

The number and scope of data privacy and security laws, regulations and other obligations is changing, subject to differing applications and interpretations, and may be inconsistent among jurisdictions, or in conflict with other data processing obligations.

Efforts to ensure that our current and future business operations and arrangements, including our relationship with our CROs or other vendors who process data on our behalf, comply with applicable data privacy and security obligations involve substantial costs.

As of December 31, 2023, we had 140 full-time employees and no part-time employees.

The majority of our employees are based at our facilities in San Jose and Milpitas, California, with a contingent of employees based outside of California.

Efforts to ensure that our current and future business operations and arrangements, including our relationship with our CROs, other vendors who process data on our behalf, and other third parties with whom we work comply with applicable data privacy and security obligations involve substantial costs.

As of December 31, 2024, we had 105 full-time employees and one part-time employee.

The majority of our employees are based at our facilities in San Jose and Fremont, California, with a contingent of employees based outside of California.

None of our employees are represented by a labor union or are a party to a collective bargaining agreement and we believe that we have good relations with our employees.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business