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Item 1. Business

2026-03-30 compared with 2025-03-27 · 346 added, 199 removed, 381 unchanged (59% of the section changed)

We are a clinical-stage biotechnology company moving towards late-stage development with a diverse portfolio of targeted and immune-mediated product candidates with the potential to be first-in-class to treat a wide range of cancers.

Our novel programs range from early research to the lead program, amezalpat (previously known as TPST-1120), that is poised to begin a pivotal study in first-line hepatocellular carcinoma (“HCC”).

In addition to amezalpat, our second clinical-stage therapeutic product candidate is TPST-1495, which we expect will enter Phase 2 development in 2025.

We are a clinical-stage biotechnology company advancing a diversified portfolio of cell therapy and small molecule product candidates.

In February 2026, we expanded our pipeline through a strategic transaction under which we acquired rights to a portfolio of dual-targeting chimeric antigen receptor T-cells (“CAR-T”) product candidates with the potential to treat certain blood cancers, solid tumors and immunology indications, including TPST-2003, an autologous CD19/B-cell maturation antigen (“BCMA”) CAR-T therapy currently in clinical development for relapsed or refractory multiple myeloma (“rrMM”).

Our portfolio also includes two clinical-stage small molecule product candidates with the potential to treat certain cancer indications.

One of our small-molecule product candidates, amezalpat (previously known as TPST-1120), has completed a Phase 2 study in first-line hepatocellular carcinoma (“HCC”).

Amezalpat remains Phase 3-ready in HCC and we plan to pursue business development discussions to advance pivotal development.

Our second small-molecule product candidate is TPST-1495, which we plan to initiate a Phase 2 study for in familial adenomatous polyposis (“FAP”), with first patient enrollment expected in 2026.

The study is expected to be funded by the National Cancer Institute (“NCI”) and conducted through the Cancer Prevention Clinical Trials Network (“CP-CTNet”), enabling advancement with limited internal capital deployment.

Our mission is to develop therapeutic products with the potential to address high unmet medical needs by identifying promising clinical-stage candidates and advancing their development to create products that will improve patients’ lives.

Recent Developments

Strategic Acquisition of Dual-Targeting CAR-T Programs

On November 19, 2025, we executed an Asset Purchase Agreement (the “Asset Purchase Agreement”) with Erigen LLC, a Delaware limited liability company (“Erigen”), and Factor Bioscience Inc., a Delaware corporation (together with Erigen, “Sellers”), pursuant to which Sellers agreed to sell and transfer to the Company all right, title and interest of Sellers, worldwide outside of China, Russia, India, and Turkey, in and to all of the assets primarily related to (a) the autologous BCMA/CD19 dual-targeting CAR T-cell therapy known as TPST-2003 currently being evaluated in a Phase 1/2a clinical study in patients with rrMM, a Phase 1/2 investigator-initiated trial (“IIT”) in patients with rrMM, and a Phase 1 clinical study in patients with POEMS Syndrome (“POEMS”), a rare blood disorder caused by abnormal plasma cells, (b) the autologous CD70/CD70 dual-targeting CAR T-cell therapy known as TPST-2206, (c) the allogeneic BCMA/CD19 dual-targeting CAR T-cell therapy with a gene edit in the TRAC locus that inactivates the T cell receptor known as TPST-3003, and (d) the allogeneic CD70/CD70 dual-targeting CAR T-cell therapy with a gene edit in the TRAC locus that inactivates the T cell receptor known as TPST-3206 (collectively referred to herein as the “Assets”), in exchange for an aggregate purchase price of 8,268,495 shares of our common stock issued to Erigen on behalf of both Sellers.

Pursuant to the Asset Purchase Agreement, at Closing we assumed Erigen’s rights and obligations under each of the Novatim License Agreement and the Restated Factor License Agreement (each as defined below under “— License and Collaboration Agreements ”).

Under the Novatim License Agreement, we obtained an exclusive license to specified patents and know-how in all fields worldwide, but excluding Greater China, India, Turkey, and Russia, to exploit the TPST-2003 and TPST-2206 programs and allogeneic CAR-T therapies based on the TPST-2003 and TPST-2206 programs.

We also received a right of first negotiation to negotiate a license to exploit allogeneic CAR-T therapies and in vivo CAR-T therapies in Greater China.

Under the Restated Factor License Agreement, we obtained an exclusive license to specified patents in all fields worldwide, but excluding Greater China, India, Turkey, and Russia, to exploit the TPST-3003 and TPST-3206 programs.

The Restated Factor License Agreement also establishes a Joint Steering Committee for the purposes of discussing and coordinating collaboration opportunities and serving as a forum for information sharing.

On February 3, 2026, we completed the acquisition of the Assets (the “Closing”) under the Asset Purchase Agreement (the “Asset Acquisition”) and issued to Erigen 8,268,495 shares of our common stock (the “Share Issuance”).

Following the transaction, we are prioritizing a capital-efficient development strategy across our portfolio.

This approach includes seeking partner support, external funding sources, and staged investment decisions based on clinical data generation and regulatory feedback.

We expect this strategy to allow us to pursue parallel development of multiple programs while managing internal cash resources and extending our operational runway.

Our product development pipeline consists of the following product candidates:

“RCC” renal cancer;

“CCA” cholangiocarcinoma;

“FPI” First Patient In;

CAR-T Cell Therapy Programs

Our cell therapy programs expand our oncology pipeline with a portfolio of next-generation CAR-T product candidates designed to potentially address the limitations of currently available cell therapies and broaden the applicability of CAR-T therapy across hematologic malignancies and solid tumors.

Our programs include autologous, allogeneic and in vivo approaches utilizing dual-targeting strategies.

Our lead cell therapy product candidate, TPST-2003, is an autologous dual-targeting CAR-T therapy directed against CD19 and BCMA for the treatment of rrMM.

In addition, our pipeline includes TPST-2206, a dual-targeting CAR-T therapy directed against CD70 for solid tumors, as well as allogeneic dual-targeting CAR-T programs, including TPST-3003 and TPST-3206, and an in vivo dual-targeting CAR-T program, TPST-4003.

We believe our cell therapy portfolio has the potential to address tumor heterogeneity and antigen escape and to improve access through scalable manufacturing approaches.

We are evaluating these programs across hematologic malignancies, solid tumors, and immunology indications.

Small-Molecule Programs

Our small-molecule programs consist of two clinical-stage product candidates with the potential to be first-in-class to treat a wide range of cancers.

Our programs include:

amezalpat (previously known as TPST-1120), that is poised to begin a pivotal study in

first-line HCC, subject to business development discussions, and TPST-1495, which we expect will enter Phase 2 development in 2026.

We believe both amezalpat and TPST-1495 are the first clinical-stage molecules designed to inhibit their respective targets.

Our philosophy is to build a company based upon not only good ideas and creative science, but also upon the efficient translation of those ideas into therapies that will improve patients’ lives.

Each of our programs are designed to provide different and independent approaches to fighting cancer, providing a portfolio of truly diversified assets.

Amezalpat (TPST-1120)

Amezalpat is an oral, small molecule, selective antagonist of peroxisome proliferator-activated receptor alpha (“PPARα”) being developed for the treatment of first-line unresectable or metastatic HCC.

In June 2024, we unveiled positive survival data from the ongoing global randomized Phase 1b/2 clinical study demonstrating that amezalpat delivered a six-month improvement in median overall survival (“OS”) with a hazard ratio (“HR”) of 0.65 when combined with atezolizumab and bevacizumab in comparison to atezolizumab and bevacizumab alone, the standard of care, in the first-line treatment of patients with unresectable or metastatic HCC.

Amezalpat remains Phase 3-ready in first-line HCC, supported by global regulatory alignment and positive randomized Phase 2 data.

We plan to pursue business development discussions to advance pivotal development.

In June 2024, we unveiled positive survival data from the global randomized Phase 1b/2 clinical study demonstrating that amezalpat delivered a six-month improvement in median overall survival (“OS”) with a hazard ratio (“HR”) of 0.65 when combined with atezolizumab and bevacizumab in comparison to atezolizumab and bevacizumab alone, the standard of care, in the first-line treatment of patients with unresectable or metastatic HCC.

Additionally, the survival benefit was preserved across key subpopulations, including patients with PD-L1 negative disease and β-catenin mutated disease, consistent with amezalpat’s proposed mechanism of action targeting both tumor cells directly and the patient’s immune system.

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In February 2025, the FDA granted Fast Track Designation (“FTD”), underscoring the agency’s recognition of the urgent need for new treatment options for HCC.

In addition to receiving ODD from the FDA, in June 2025, the European Medical Agency (“EMA”) also granted ODD for the treatment of patients with HCC.

These designations provide potential regulatory benefits, including increased engagement with the FDA, eligibility for accelerated approval and priority review, and, for ODD, potential market exclusivity upon approval.

We continue to advance amezalpat’s clinical development in alignment with both the FDA and the European Medicines Agency (“EMA”) and are actively preparing for the initiation of our pivotal Phase 3 study.

Our second clinical program, TPST-1495, is a novel, small-molecule dual antagonist of the EP2 and EP4 receptors of prostaglandin E2 (“PGE2”), a pathway implicated in multiple cancers.

Our development strategy for TPST-1495 includes evaluation in Familial Adenomatous Polyposis (“FAP”), a rare genetic disorder that significantly increases the risk of gastrointestinal cancers and for which there are no approved systemic therapies.

Given that prostaglandin signaling is also

implicated in FAP and based on positive preclinical data in a relevant mouse model, we believe there is strong mechanistic support for this approach.

In March 2025, the Cancer Prevention Clinical Trials Network (“CP-CTNet”) received a “Study May Proceed” letter from the FDA, authorizing the initiation of a National Cancer Institute (“NCI”)-funded Phase 2 clinical trial evaluating TPST-1495 in patients with FAP.

Our second clinical-stage small-molecule program, TPST-1495, is a novel, dual antagonist of the EP2 and EP4 receptors of prostaglandin E2 (“PGE2”), a pathway implicated in multiple cancers.

Our development strategy for TPST-1495 includes evaluation in FAP, a rare genetic disorder that significantly increases the risk of gastrointestinal cancers and for which there are no approved systemic therapies.

Given that prostaglandin signaling is also implicated in FAP and based on positive preclinical data in a relevant mouse model, we believe there is strong mechanistic support for this approach.

In March 2025, the CP-CTNet received a “Study May Proceed” letter from the FDA, authorizing the initiation of a NCI-funded Phase 2 clinical trial evaluating TPST-1495 in patients with FAP.

This trial, run by CP-CTNet and financially supported by the NCI’s Division of Cancer Prevention, underscores the urgent need for innovative cancer prevention strategies in high-risk patient populations.

The Phase 2 study is expected to begin in 2026.

Beyond these clinical programs, we plan to continue to leverage our drug development and company-building experience along with academic relationships to identify promising new targets that have the potential to feed new programs into our pipeline.

Our Discovery Research team employs a multidisciplinary approach to identify and validate therapeutic targets in oncology, and preclinical validation studies are then conducted to further understand the mechanism of action and potential therapeutic benefit to patients.

Our product development pipeline consists of the following orally available therapies, which if approved by the FDA, we believe will be first in class:

Timing is an estimate based on current projections and status of programs.

For amezalpat, Phase 3 timelines are subject to funding.

A per-protocol planned analysis at 70% of events, prior to full data analysis.

Dependent on additional funding.

To be operationalized by the Cancer Prevention Network of NCI.

Our team has come together to build an integrated company to deliver meaningful therapies to cancer patients by leveraging our collective capabilities and experience.

We expect to build value for our stockholders with the following over-arching strategy:

• Advance amezalpat into a pivotal Phase 3 study in first-line HCC patients where amezalpat will be studied in a combination treatment and compared to a standard-of-care therapy.

We believe the continued positive results from the ongoing randomized Phase 1b/2 study provides strategic opportunities for us, and we received positive feedback from

the FDA on the pivotal Phase 3 clinical trial design.

We are also evaluating further development in RCC and CCA based on the Phase 1 data presented at ASCO 2022.

• Explore TPST-1495 in a Phase 2 study in patients with FAP with CP-CTNet in 2025.

• Enhance our pipeline by identifying novel oncology targets and in-licensing opportunities.

Although we believe we have a robust pipeline, we continue to evaluate and pursue novel targets and product candidates for acquisition and in-licensing to supplement our internal research efforts and further build our pipeline of targeted molecules for oncology.

Through our team’s focus and expertise in oncology and immunology, as well as established relationships with oncology and immunology thought leaders, we believe we are positioning the company as a partner of choice for innovative oncology drug candidate development.

Continued advances in the biological understanding of diseases should provide opportunities to further expand our portfolio with preclinical and/or clinical product candidates.

• Explore business development opportunities to maximize the potential of our pipeline and extend financial resources.

We believe that our pipeline has broad potential reach and partnerships that bring in additional expertise and/or geographic presence could be important to increase the likelihood of success.

We currently own all rights to our programs.

We intend to become a fully integrated biopharmaceutical company and build a targeted sales force in the United States to support the commercialization of our drug candidates, if approved.

Clinical Programs

Our objective is to build a capital-efficient oncology company by advancing a pipeline of advanced CAR-T cell therapy and small-molecule product candidates through clinical development while maintaining disciplined capital allocation.

Our strategy includes the following components:

• Advance TPST-2003 through upcoming clinical milestones

We plan to continue development of TPST-2003 with near-term clinical data expected from an ongoing Phase 1/2a clinical trial in China.

We anticipate initiation of a registrational Phase 2b in China by the end of 2026, with interim data expected in 2027.

Development activities in China are funded by our strategic partner, Novatim Immune Therapeutics (“Novatim”), providing access to pivotal data while preserving internal capital.

• Expand the portfolio with allogeneic and in vivo CAR-T development

TPST-3003 and TPST-4003 represent our first allogeneic and in vivo CAR-T programs, respectively, and are each designed to extend the TPST-2003 biology into potentially more scalable and patient-friendly modalities.

We expect to advance these programs through preclinical development and evaluate potential clinical entry through strategic partner-funded IIT clinical studies in the near term.

• Position amezalpat for pivotal development through business development

Amezalpat remains Phase 3-ready in first-line HCC, supported by global regulatory alignment and positive randomized Phase 2 data.

We plan to pursue business development discussions to advance pivotal development.

• Advance TPST-1495 through externally funded clinical development

We plan to initiate a Phase 2 study of TPST-1495 in FAP, with first patient enrollment expected in 2026.

The study is expected to be funded by the NCI and conducted through the Cancer Prevention Clinical Trials Network, enabling advancement with limited internal capital deployment.

• Advance a diversified next-generation CAR-T pipeline

We plan to progress additional dual-targeting CAR-T programs that broaden the platform across modalities and indications, including:

a dual-targeting CD70/CD70 CAR-T

an allogeneic dual-targeting CD70/CD70 CAR-T

CAR-T Cell Therapy

Background on Cancer and CAR-T Cell Therapy

Cancer remains a leading cause of death worldwide and continues to represent a significant unmet medical need despite advances in surgery, radiation, targeted therapies and immunotherapies.

Hematologic malignancies, including multiple myeloma and certain lymphomas and leukemias, often have limited treatment options in relapsed or refractory settings, where outcomes remain poor.

Similarly, many solid tumors, including renal cell carcinoma, remain difficult to treat in advanced stages, particularly following progression on standard therapies.

Adoptive cell therapy, including CAR-T, has emerged as an important treatment modality in oncology.

CAR-T therapy typically involves collecting a patient’s T cells, genetically modifying them to express engineered receptors that recognize tumor-associated antigens, expanding the modified cells ex vivo, and infusing them back into the patient to target cancer cells.

CAR-T therapies have demonstrated meaningful clinical responses in certain hematologic malignancies and have led to multiple regulatory approvals.

However, currently available CAR-T therapies face limitations, including antigen escape, limited durability of response, manufacturing complexity, safety risks and reduced efficacy in certain patient populations.

Next-generation CAR-T approaches are being developed to address these limitations.

These include dual-targeting CAR-T therapies designed to recognize multiple tumor antigens, which may help mitigate antigen escape and improve durability, as well as allogeneic and in vivo CAR-T therapies designed to improve manufacturing scalability and patient access.

CD19/BCMA Dual-Targeting CAR-T Therapy in rrMM

Our lead cell therapy product candidate, TPST-2003, is an autologous dual-targeting CAR-T therapy directed against CD19 and BCMA for the treatment of rrMM.

Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of

malignant plasma cells in the bone marrow.

Despite advances in treatment, including proteasome inhibitors, immunomodulatory agents and monoclonal antibodies, patients with relapsed or refractory disease often experience progressive disease and poor outcomes.

While currently approved CAR-T therapies targeting BCMA have demonstrated clinical benefit in rrMM, disease relapse remains common, and treatment options following relapse are limited.

BCMA is a cell surface receptor that is preferentially expressed on mature B cells and plasma cells, including malignant plasma cells in multiple myeloma, and plays an important role in plasma cell survival and proliferation.

As a result, BCMA has emerged as a clinically validated target for CAR-T therapy in multiple myeloma.

However, resistance to BCMA-targeted therapies has been observed, including through antigen loss or downregulation, which may contribute to disease relapse.

CD19 is a B-cell lineage antigen that is expressed earlier in B-cell development and has been implicated in certain subsets of multiple myeloma, including progenitor or disease-propagating cell populations.

Targeting both CD19 and BCMA simultaneously may help address tumor heterogeneity and reduce the risk of antigen escape.

Preclinical and clinical studies reported in the scientific literature have suggested that dual-targeting approaches may improve depth and durability of response compared to single-target therapies.

This body of literature provides the scientific rationale for the development of dual-targeting CAR-T therapies such as TPST-2003 for the treatment of patients with rrMM.

Dual-Targeting BCMA/CD19 Autologous CAR-T Therapy

TPST-2003 is an autologous, dual-targeting CAR-T therapy designed to target both BMCA and CD19.

TPST-2003 is being developed for the treatment of rrMM.

Mechanism of Action

TPST-2003 incorporates a proprietary parallel dual-targeting CAR architecture designed to recognize both BCMA and CD19.

TPST-2003 parallel dual-targeting CAR construct targeting BCMA and CD19.

Scientific Rationale for Dual-Targeting CAR Architecture

CAR-T therapies function by engineering a patient’s T cells to express receptors that recognize tumor-associated antigens.

Most currently available CAR-T therapies in multiple myeloma target a single antigen, typically BCMA.

While these therapies can produce deep responses, relapse may occur when tumor cells reduce or lose expression of that antigen or when heterogeneous tumor populations express different surface markers.

By enabling recognition of two distinct targets, TPST-2003’s dual-targeting approach is intended to:

• Reduce the likelihood of tumor escape through antigen loss;

• Improve targeting of heterogeneous tumor populations;

• Potentially enhance persistence of anti-tumor activity.

Clinical responses have been observed across multiple dose levels and study settings to date;

however, additional follow-up and larger studies will be required to determine the reproducibility and durability of these findings.

The same dual-targeting CAR architecture forms the basis of additional programs in our pipeline, including TPST-3003, an allogeneic CAR-T program, and TPST-4003, an in vivo CAR-T approach.

The clinical studies described below were designed to evaluate the safety and clinical activity of this dual-targeting approach, including in heavily pretreated patients.

Clinical Study Design

TPST-2003 is currently being evaluated in a Phase 1/2 IIT clinical study and a REDEEM-1 Phase 1/2a trial, in each case in patients with rrMM, including patients who have received multiple prior lines of therapy.

The IIT and REDEEM-1 Phase 1/2a trial are being conducted by investigators affiliated with Novatim and are being funded by Novatim.

To be eligible for the Phase 1/2 IIT clinical study and the REDEEM-1 Phase 1/2a trial, patients must have rrMM and must have received at least one prior line of therapy.

The Phase 1/2 IIT clinical study and the REDEEM-1 Phase 1/2a trial are primarily focused on evaluating the safety and tolerability of TPST-2003, as well as determining the clinical recommended dose of TPST-2003.

Accordingly, the primary endpoints of the Phase 1/2 IIT clinical study and the REDEEM-1 Phase 1/2a trial are the assessment of adverse events (“AEs”) and serious adverse events (“SAEs”).

The secondary endpoints cover both PK and PD assessments, examining how the therapy behaves and acts within the body, as well as a set of efficacy measures including:

progression-free survival (“PFS”);

overall response rate (“ORR”);

complete response (“CR”);

strict complete response (“sCR”);

duration of response;

disease control rate (“DCR”), minimal residual disease (“MRD”);

Clinical Development Program

Clinical experience with TPST-2003 to date consists of early-phase studies, including the ongoing Phase 1/2 IIT and the ongoing REDEEM-1 Phase 1/2a trial.

As of the January 31, 2026 data cutoff, a total of 36 patients with rrMM had received one infusion of TPST-2003 across these two studies:

• 24 patients treated in the Phase 1/2 IIT;

• 12 patients treated in the REDEEM-1 Phase 1/2a trial.

Patients enrolled in REDEEM-1 had received a median of four prior lines of therapy.

Among the six patients evaluable for efficacy as of the January 31, 2026 data cutoff in REDEEM-1, including three treated at dose level 1 (1 x 10 6 cells/kg) and three treated at dose level 2 (2 x 10 6 cells/kg), the CR rate was 100% (6/6) based on International Myeloma Working Group criteria.

Across both studies, among 25 evaluable patients with measurable disease at baseline, the ORR was 100% (25/25).

These findings are based on a limited number of patients to date, and additional follow-up will be required to determine clinical benefit.

Safety Profile Observations to Date

The safety profile observed in REDEEM-1 has included:

• No Grade 3 or higher cytokine release syndrome (“CRS”);

• One patient treated at the highest dose level experiencing low-grade immune effector cell-associated neurotoxicity syndrome (“ICANS”);

• No Grade 3 or higher ICANS.

We believe that the observed safety profile together with the consistency of responses observed in the REDEEM-1 trial support our plan to accelerate our development timeline and meet with the FDA to discuss initiating a U.S.

registrational study later this year.

Durability of Response Observed in Earlier Study

We believe clinical findings from the REDEEM-1 study appear generally consistent with the earlier IIT.

In the IIT, among 19 evaluable patients with measurable disease at baseline:

• ORR was 100% (19/19);

• CR rate was 89.5% (17/19);

• At the highest evaluated dose level, CR was observed in 100% (5/5).

The IIT also reported durable disease control, including:

• Median PFS of 23.1 months across all patients;

• Median PFS of 23.1 months in patients with extramedullary disease (“EMD”);

• MRD negativity at month 12 in all evaluable patients (5/5).

Patients with EMD are often associated with poorer outcomes and shorter disease control in rrMM.

We are continuing to evaluate the durability of response observed in these studies.

TPST-2003 is also currently being evaluated in an ongoing Phase 1 clinical trial in patients with POEMS, a rare blood disorder caused by abnormal plasma cells.

The POEMS trial is being conducted by investigators affiliated with Novatim and is being sponsored by Novatim.

Development Plans

We expect to present additional results from the REDEEM-1 study and updated IIT data at a scientific meeting in 2026.

Based on data generated to date, we plan to submit an Investigational New Drug (“IND”) application to the FDA and, subject to regulatory clearance, may initiate a U.S.

registrational study in 2026.

Pre-Clinical Programs

Allogeneic Dual-Targeting CD19/BCMA CAR-T

Allogeneic CAR-T cell therapies are manufactured from donor cells, unlike autologous CAR-T cell therapies, which are manufactured from the patient’s own cells.

Allogeneic CAR-T cell therapies thus have the potential to offer an off-the-shelf alternative to autologous products, that may reduce manufacturing complexity, potentially increasing availability to patients.

To manufacture an allogeneic CAR-T cell therapy, the T-cell receptor of the donor cells is typically eliminated (“knocked out”), to reduce the chance that the donor cells may nonspecifically attack the patient’s healthy cells (“graft-vs-host activity”).

TPST-3003 is an allogeneic dual-targeting CD19/BCMA CAR-T product that we are developing for the treatment of rrMM.

Because TPST-3003 uses the same dual-targeting architecture as TPST-2003, we believe that TPST-3003 has the potential to maintain the same positive safety and efficacy profile that we have observed in early-stage clinical studies of TPST-2003, while reducing manufacturing complexity and potentially increasing availability to patients.

We are planning to evaluate TPST-3003 in patients with rrMM in an strategic partner-sponsored IIT, with enrollment potentially beginning in the third quarter of 2026.

In-vivo Dual-Targeting CD19/BCMA CAR-T

In vivo CAR-T therapies typically comprise nucleic acid molecules that encode a CAR sequence and which are formulated for delivery to a patient’s T cells in the patient’s body.

Most typically, an in vivo CAR-T therapy consists of one or more mRNA molecules encoding a CAR sequence, formulated as a lipid nanoparticle, which is designed to target delivery to a specific type of cell in a patient’s body (e.g., a T cell that expresses the CD8 protein).

Because in vivo CAR-T therapies generally do not require manipulating either the patient’s or a donor’s cells as part of the manufacturing process, they have the potential to reduce manufacturing complexity as compared to both autologous and allogeneic CAR-T approaches.

Because of the potential advantages of in vivo CAR-T therapies, these approaches are being explored for potential treatment of immunology indications, including lupus, in addition to cancer.

TPST-4003 is an in vivo dual-targeting CD19/BCMA CAR-T product that we are developing for the treatment of lupus.

Because TPST-4003 uses the same dual-targeting architecture as TPST-2003, we believe that TPST-4003 has the potential to achieve a

favorable safety and efficacy profile as compared with single-targeting approaches.

We are planning to evaluate TPST-4003 in patients with lupus in a strategic partner-sponsored IIT, with enrollment potentially beginning in the second quarter of 2026.

Autologous Dual-Targeting CD70/CD70 CAR-T

CD70 is a protein that is often expressed on the surface of cells that make up a solid tumor, including in patients with renal cell carcinoma (“RCC”).

While therapeutic approaches targeting CD70 have shown promise across various experimental settings, some cancer cells within a solid tumor may only express low levels of CD70, while other cancer cells may downregulate expression of CD70 during treatment with a CD70-targeting therapy.

TPST-2206 is an autologous dual-targeting CD70/CD70 CAR-T product that we are developing for the treatment of RCC.

TPST-2206 uses the same dual-targeting architecture as TPST-2003, but replaces the CD19 and BCMA-targeting CARs with two CD70-targeting CARs.

We believe that this dual-targeting structure may allow TPST-2206 to more effectively target and treat CD70-expressing solid tumors than single-targeting approaches.

TPST-2206 is being evaluated in pre-clinical studies with a Phase 1 clinical trial of TPST-2206 in patients with RCC planned to begin in the second quarter of 2026.

These pre-clinical activities and the planned Phase 1 clinical trial are being conducted and sponsored by our strategic partner, Novatim.

We are planning to review the results of these studies, and, depending on those data, evaluate the potential to develop TPST-2206 in countries other than China, India, Turkey, and Russia.

Allogeneic Dual-Targeting CD70/CD70 CAR-T

TPST-3206 is an allogeneic dual-targeting CD70/CD70 CAR-T product that we are developing for the treatment of RCC.

TPST-3206 uses the same dual-targeting structure as TPST-2206 and the same manufacturing approach as our other allogeneic CAR-T program, TPST-3003.

We are planning to review the results of the ongoing pre-clinical and planned clinical evaluation of TPST-2206, which is being conducted and sponsored by Novatim, and, depending on those data, evaluate the potential to develop TPST-3206 in countries other than China, India, Turkey, and Russia.

Small Molecule Programs

PPARα Transcription Factor Antagonist

Amezalpat, a potentially first-in-class oral small molecule antagonist of PPARα, has completed a Phase 1a/b trial, and is currently being studied in an ongoing randomized Phase 1b/2 trial.

Amezalpat, a potentially first-in-class oral small molecule antagonist of PPARα, has completed a Phase 1a/b trial, and a global randomized Phase 1b/2 trial.

The Phase 1a/b trial was a multicenter, open-label, dose-escalation, that evaluated amezalpat as both a monotherapy and combination therapy with nivolumab in patients with advanced solid tumors.

Results from both the monotherapy and combination arms were presented in an oral presentation at the ASCO conference in 2022.

The ongoing Phase 1b/2 trial is a randomized, multicenter, global study in collaboration with Roche that is evaluating amezalpat in combination with atezolizumab (TECENTRIQ®) and bevacizumab (Avastin®) in previously untreated patients with advanced HCC, compared to atezolizumab and bevacizumab alone, which is a standard of care for that indication and patient population.

As of an updated February 14, 2024 data cutoff date, the ongoing global randomized Phase 1b/2 trial continued to show positive outcomes in patients with advanced or metastatic HCC who received the amezalpat combination therapy as compared to the control arm, including a survival benefit in both the overall population and key subpopulations.

The Phase 1b/2 trial was a randomized, multicenter, global study in collaboration with Roche that was evaluating amezalpat in combination with atezolizumab (TECENTRIQ®) and bevacizumab (Avastin®) in previously untreated patients with advanced HCC, compared to atezolizumab and bevacizumab alone, which is a standard of care for that indication and patient population.

As of an updated February 14, 2024 data cutoff date, the global randomized Phase 1b/2 trial continued to show positive outcomes in patients with advanced or metastatic HCC who received the amezalpat combination therapy as compared to the control arm, including a survival benefit in both the overall population and key subpopulations.

Tumors evolve to promote their own survival by alternating energy sources, promoting angiogenesis and evading immune recognition.

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Overview of amezalpat Clinical Trials

We completed a Phase 1a/b study of amezalpat and a randomized Phase 1b/2 clinical study is ongoing.

We completed a Phase 1a/b study and a global randomized Phase 1b/2 clinical study of amezalpat.

We have released positive data from both studies, and we believe the continued positive data announced in 2024 supports the advancement of amezalpat to a pivotal Phase 3 trial in first-line HCC.

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Randomized Data in HCC

As of an updated February 14, 2024 data cutoff date, the ongoing global randomized Phase 1b/2 trial of amezalpat, combined with the standard-of-care first-line regimen of atezolizumab and bevacizumab continued to show positive results in patients with advanced or metastatic HCC.

As of an updated February 14, 2024 data cutoff date, the global randomized Phase 1b/2 trial of amezalpat, combined with the standard-of-care first-line regimen of atezolizumab and bevacizumab continued to show positive results in patients with advanced or metastatic HCC.

The study is comparing the amezalpat arm to standard of care alone, and enrolled 40 patients randomized to the amezalpat arm and 30 patients randomized to the control arm.

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Data not provided by Roche

Additionally in biomarker subpopulation analyses, patients with b-catenin activating mutations (21% of the study population) showed an increased confirmed ORR of 43% and a disease control rate (“DCR”) of 100% in the amezalpat arm.

Additionally in biomarker subpopulation analyses, patients with b-catenin activating mutations (21% of the study population) showed an increased confirmed ORR of 43% and a DCR of 100% in the amezalpat arm.

The triplet regimen with amezalpat remained active across PD-L1 negative tumors, with a confirmed ORR of 27% in the amezalpat arm, compared to a reduced ORR of 7% for the control arm.

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Dual EP2/EP4 Prostaglandin Receptor Antagonist

Our second clinical product candidate is TPST-1495, a potentially first-in-class, oral, small molecule dual antagonist of the prostaglandin E2 (“PGE2”), receptors, EP2 and EP4.

Our second small-molecule product candidate is TPST-1495, a potentially first-in-class, oral, small molecule dual antagonist of the prostaglandin E2 (“PGE2”), receptors, EP2 and EP4.

TPST-1495 is engineered to inhibit only these receptors while sparing the homologous - but differentially active - EP1 and EP3 receptors.

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TPST-1495 was evaluated in a first-in-human, Phase 1, multicenter, open-label, schedule and dose optimization trial in subjects with late-stage solid tumor cancers that are deemed incurable.

Study objectives include evaluation of safety, tolerability, PK, PD, and preliminary anti-tumor activity of TPST-1495 as monotherapy and in combination with the checkpoint inhibitor, pembrolizumab.

TPST-1495 has been evaluated on a once daily (“QD”) or twice daily (“BID”) schedule and with continuous

or intermittent administration as monotherapy and in combination with pembrolizumab.

Study objectives include evaluation of safety, tolerability, PK, PD, and preliminary anti-tumor activity of TPST-1495 as monotherapy and in combination with the checkpoint inhibitor,

pembrolizumab.

TPST-1495 has been evaluated on a once daily (“QD”) or twice daily (“BID”) schedule and with continuous or intermittent administration as monotherapy and in combination with pembrolizumab.

Results from the Phase 1 study were presented at ASCO 2023.

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As of December 31, 2025, we own worldwide rights to TPST-1495, and our issued United States patents covering TPST-1495 as compositions of matter, pharmaceutical compositions and related methods of use, are expected to expire between April 2038 and April 2039, without giving effect to any patent term adjustments or patent term extensions for regulatory delay.

Discovery Research

Our Discovery Research team is dedicated to identifying and validating novel therapeutic targets in oncology.

We are not bound to a single technology platform, which allows us the scientific freedom to pursue targets and modalities that we believe have the highest probability to benefit patients.

Rigorous medicinal chemistry and a broad set of preclinical validation studies are conducted to further evaluate lead compounds and inform decision-making for advancement into clinical development.

Collaboration with academic institutions, contract research organizations (“CROs”), and strategic partners provides opportunity to enrich our pipeline, as well, enhancing our ability to deliver innovative medicines to address unmet medical needs.

License Agreements

License and Collaboration Agreements

Novatim License and Collaboration Agreement

On July 18, 2025, Erigen entered into an Exclusive License and Collaboration Agreement (the “Novatim License Agreement”) with Novatim.

On February 3, 2026, the Novatim License Agreement was assigned to us in connection with the Closing pursuant to the Asset Purchase Agreement.

Pursuant to the Novatim License Agreement, we obtained an exclusive license to specified patents and know-how in all fields worldwide, but excluding Greater China, India, Turkey, and Russia, to exploit the TPST-2003 and TPST-2206 programs and allogeneic CAR-T therapies based on the TPST-2003 and TPST-2206 programs.

We also received a right of first negotiation to negotiate a license to exploit allogeneic CAR-T therapies and in vivo CAR-T therapies in Greater China.

We are obligated to meet certain diligence milestones by specified dates and to use commercially reasonable efforts to develop and make commercially available at least one licensed product in the licensed territory.

No upfront payment was paid pursuant to the Novatim License Agreement.

We are obligated to pay Novatim up to $80 million in total upon achievement of certain development milestones for the programs and up to $1.24 billion in total upon achievement of certain commercial milestones for the programs.

In addition, we are required to pay Novatim mid-to-high single digit royalties on net sales of licensed products, subject to certain customary reductions, up to a lifetime maximum of $800 million, following which our license shall become fully paid and royalty-free.

The Novatim License Agreement is subject to termination (i) by either party, subject to specified cure periods, for the material breach by the other party or the bankruptcy or insolvency of the other party, or (ii) by mutual agreement of the parties.

Factor Amended and Restated License and Collaboration Agreement

On November 19, 2025, Erigen entered into an Amended and Restated License and Collaboration Agreement (the “Restated Factor License Agreement”) with Factor Bioscience Limited.

On February 3, 2026, the Restated Factor License Agreement was assigned to us in connection with the Closing pursuant to the Asset Purchase Agreement.

Pursuant to the Restated Factor License Agreement, we obtained an exclusive license to specified patents in all fields worldwide, but excluding Greater China, India, Turkey, and Russia (the “Licensed Territory”), to exploit the TPST-3003 and TPST-3206

The Restated Factor License Agreement also established a Joint Steering Committee for the purposes of discussing and coordinating collaboration opportunities and serving as a forum for information sharing.

No upfront payment was paid pursuant to the Restated Factor License Agreement.

We are obligated to pay Factor Bioscience Limited up to $40 million in total upon achievement of certain development milestones for the programs and up to $620 million in total upon achievement of certain commercial milestones for the programs.

In addition, we are required to pay Factor Bioscience Limited mid-single digit to high-teens royalties on net sales of licensed products on a country-by-country and licensed product-by-licensed product basis until expiration of the last to expire valid claim of certain licensed patents covering such licensed product in such country, subject to certain customary reductions, and low-to-mid double digit sublicense fees.

The Restated Factor License Agreement will continue until expiration of the last-to-expire Royalty Term.

“Royalty Term” is defined as, on a product-by-product and country-by-country basis, the period commencing on the first arms-length sale of a product in a country of the Licensed Territory, and ending on the date of expiration of the last to expire valid patent covering the exploitation of the applicable product in the applicable country of the Licensed Territory.

The Restated Factor License Agreement is subject to termination (i) by either party, subject to specified cure periods, for the material breach by the other party or the bankruptcy or insolvency of the other party, (iii) by us for any reason upon 60 days notice, or (iii) by mutual agreement of the parties.

Factor Amended and Restated Master Services Agreement

On November 19, 2025, Erigen entered into an Amended and Restated Master Services Agreement (the “Restated Factor Services Agreement”) with Factor.

On February 3, 2026, the Restated Factor Services Agreement was assigned to us in connection with the Closing pursuant to the Asset Purchase Agreement.

Pursuant to the Restated Factor Services Agreement, Factor will perform services requested by us on a fee-for-services basis and provide us access to Factor’s facilities as mutually agreed upon in one or more written work orders.

All deliverables developed as a result of Factor’s performance of the services or as set forth in a work order, other than specified improvements, will be our property and confidential information.

Furthermore, Factor granted us a freedom-to-operate license to its background intellectual property, excluding certain technology and improvements licensed under the Restated Factor License Agreement, solely to the extent necessary or reasonably useful to use, practice or otherwise exploit the deliverables.

Either party may terminate the Restated Factor Services Agreement at any time without cause upon 30 days’ notice, provided that termination of the Restated Factor Services Agreement will not terminate any ongoing work orders.

Either party may terminate individual work orders in accordance with the terms of the applicable work order.

Roche Collaboration Agreement

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Each party has the right to terminate the collaboration agreement upon 60 days prior written notice to the other party.

Upon any termination of the agreement, neither we nor Roche will be entitled to any compensation, damages or other payment.

Upon any termination

of the agreement, neither we nor Roche will be entitled to any compensation, damages or other payment.

If any individual study supplement is terminated, Roche must return all unused amezalpat to us free of charge or destroy such product at our request.

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Under the Roche Supply Agreement, the parties may execute one or more clinical supply agreement supplements (each, a “CSA Supplement”) that will set forth the study to be conducted by us, the quantities of atezolizumab to be supplied by Roche for such study, and the delivery timeline for such quantities of atezolizumab.

In October 2024, we entered into a CSA Supplement for Roche to supply atezolizumab to us, free of charge, for use in our planned Phase 3 trial.

In October 2024, we entered into a CSA Supplement for Roche to supply atezolizumab to us, free of charge, for use in a potential Phase 3 trial.

Sales and Marketing

We intend to retain significant development and commercial rights to our product candidates and, if marketing approval is obtained, to commercialize our product candidates on our own, or potentially with a partner, in the United States and other regions.

We intend to retain significant development and commercial rights to our product candidates and, if marketing approval is obtained, to commercialize our product candidates with a partner, in the United States and other regions.

We currently have no sales, marketing or commercial product distribution capabilities.

We intend to build the necessary infrastructure and capabilities over time for the United States, and potentially other regions, following further advancement of our product candidates.

Clinical data, the size of the addressable patient population, the size of the commercial infrastructure and manufacturing needs may all influence or alter our commercialization plans.

If we build a commercial infrastructure to support marketing in North America, such commercial infrastructure could be expected to include a targeted sales force supported by sales management, internal sales support, an internal marketing group and distribution support.

To develop the appropriate commercial infrastructure internally, we would have to invest financial and management resources, some of which would have to be deployed prior to any confirmation that one of our product candidates will be approved.

Manufacturing

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While we believe that our technology, development experience and scientific knowledge provide us with competitive advantages, we face potential competition from many different sources, including large and specialty pharmaceutical and biotechnology companies, academic research institutions, government agencies and public and private research institutions that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing and commercialization.

If amezalpat, TPST-1495, or any future product candidates are approved for the treatment of tumors, they may compete with other products used to treat such diseases.

If our current or any future product candidates are approved for the treatment of cancer, they may compete with existing therapies as well as product candidates currently in development.

There are a variety of treatments used for cancerous tumors that include chemotherapy drugs, small molecules, monoclonal antibodies, antibody-drug conjugates, bi-specific antibodies, cell therapies, oncolytic viruses and vaccines, as well as other approaches.

In addition, there are several competitors in clinical development for the treatment of

HCC, RCC, cholangiocarcinoma, and other indications that we may be targeting with amezalpat and TPST-1495, including companies such as Ono, Adlai Nortye, Merck, Roche, Exelixis, and AstraZeneca.

Amezalpat, our small molecule designed to be a selective antagonist of PPARα, is the first PPARα antagonist in the clinic.

In addition, there are several competitors in clinical development for

the treatment of HCC, RCC, cholangiocarcinoma, and other indications that we may target with TPST-1495, and amezalpat, including companies such as Ono, Adlai Nortye, Merck, Roche, Exelixis, and AstraZeneca.

In the field of cell therapies, there are several competitors developing CAR-T and other cellular therapies for the treatment of system lupus erythematosus (SLE), multiple myeloma, and other hematologic malignancies that we may target with TPST-2003, TPST-3003 and TPST-4003, including companies such as Johnson & Johnson, Bristol Meyers Squibb, Gilead Sciences, Arcellx, Legend Biotech, Allogene, Cellectis, AstraZeneca and other biotechnology and pharmaceutical companies developing BCMA-targeting and dual-targeting cell therapies.

TPST-2003, our dual-targeting CD19/BCMA CAR-T cell therapy is, to our knowledge, the first parallel structure CD19/BCMA dual-targeting CAR-T under development for the treatment of rrMM specifically targeting patients with EMD.

We are aware of other clinical-stage CD19/BCMA dual-targeting CAR-T product candidates, including a product under development by AstraZeneca.

We are also aware of several approved therapies and products under development that utilize either a CD19 or BCMA single-targeting CAR structure.

Amezalpat, our small molecule designed to be a selective antagonist of PPARα, is, to our knowledge, the first PPARα antagonist to enter the clinic.

We are not aware of other companies developing such an antagonist.

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and to operate without infringing on the valid and enforceable patents and other proprietary rights of third parties.

As of December 31, 2024, our patent portfolio consisted of issued patents and pending patent applications that we own or in-licensed related to amezalpat, TPST-1495 and various other compounds and programs, such as our earlier-stage research programs.

In total, as of the same date, we owned or in-licensed nine issued United States patents, eleven pending United States patent applications, four pending Patent Cooperation Treaty (PCT) applications, and in various markets outside of the United States, including Europe, China and Japan:

With respect to TPST-2003, as of February 28, 2026, our in-licensed patent portfolio included one pending U.S.

patent application, and nine pending patent applications in various markets outside of the United States, including Europe and Japan.

The pending patent applications cover TPST-2003 as compositions of matter, pharmaceutical compositions, and related methods of use.

Any patents that may issue from the pending patent applications are expected to expire in March 2044, absent any patent term adjustments or patent term extensions for regulatory delay.

With respect to TPST-2206, as of February 28, 2026, our in-licensed patent portfolio included two pending PCT applications.

The pending PCT applications cover TPST-2206 as compositions of matter, pharmaceutical compositions and related methods of use.

Any patents that may issue from the pending PCT applications are expected to expire in July 2045, absent any patent term adjustments or patent term extensions for regulatory delay.

With respect to our TPST-3003, TPST-3206, and TPST-4003 programs, as of February 28, 2026, our in-licensed patent portfolio included ten issued U.S.

patents, four pending U.S.

patent applications, one pending PCT application, and five issued patents and eight pending patent applications in various markets outside of the United States, including Europe and Japan.

The issued U.S.

patents are expected to expire in May 2032, absent any patent term adjustments or patent term extensions for regulatory delay.

Any additional patents that may issue from these pending patent applications are expected to expire between May 2032 and April 2045, absent any patent term adjustments or patent term extensions for regulatory delay.

As of December 31, 2025, our patent portfolio consisted of issued patents and pending patent applications that we own related to amezalpat and TPST-1495.

In total, as of the same date, we owned ten issued United States patents, four pending United States patent applications, one pending Patent Cooperation Treaty (“PCT”) application, and in various markets outside of the United States, including Europe, China and Japan:

68 issued patents and 8 pending patent applications.

With respect to amezalpat, as of December 31, 2024, we own issued patents and pending patent applications in the United States, Europe, China, Japan, and other markets outside of the United States as well as one pending PCT application.

With respect to amezalpat, as of December 31, 2025, we owned issued patents and pending patent applications in the United States, Europe, China, Japan, and other markets outside of the United States as well as one pending PCT application.

The issued United States patents covering amezalpat as compositions of matter, pharmaceutical compositions, and related methods of use are expected to expire in December 2033, absent any patent term adjustments or patent term extensions for regulatory delay.

Any additional patents that may issue from these pending patent applications are expected to expire between December 2033 and May 2045, absent any patent term adjustments or patent term extensions for regulatory delay.

With respect to TPST-1495, as of December 31, 2024, we own issued patents and pending patent applications in the United States, Europe, China, Japan, and other markets outside of the United States as well as one pending PCT application.

Any additional patents that may issue from these pending patent applications are expected to expire between December 2033 and March 2046, absent any patent term adjustments or patent term extensions for regulatory delay.

With respect to TPST-1495, as of December 31, 2025, we owned issued patents and pending patent applications in the United States, Europe, China, Japan, and other markets outside of the United States.

The issued United State patents covering TPST-1495 as compositions of matter, pharmaceutical compositions, and related methods of use are expected to expire between April 2038 and April 2039, absent any patent term adjustments or patent term extensions for regulatory delay.

Any additional patents that may issue from these pending patent applications are expected to expire between April 2038 and June 2045, absent any patent term adjustments or patent term extensions for regulatory delay.

As of December 31, 2024, our patent portfolio also included pending patent applications in the United States and Europe that are exclusively licensed to us by the University of California at Berkeley.

The licensed patent applications do not cover any of our current product candidates.

Any additional patents that may issue from these pending patent applications are expected to expire between April 2038 and April 2039, absent any patent term adjustments or patent term extensions for regulatory delay.

We also possess substantial know-how and trade secrets relating to the development and commercialization of our product candidates, including related manufacturing processes and technology.

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The restoration period cannot be longer than five years and the total patent term, including the restoration period, must not exceed 14 years following FDA approval.

The term of patents outside of the United States varies in accordance with the laws of the foreign jurisdiction but typically is also 20 years from the earliest effective filing date.

The term of patents outside of the

United States varies in accordance with the laws of the foreign jurisdiction but typically is also 20 years from the earliest effective filing date.

However, the actual protection afforded by a patent varies on a product-by-product basis, from country-to-country and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent.

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FDA Approval Process

In the United States, pharmaceutical products are subject to extensive regulation by the FDA, the Federal Food, Drug, and Cosmetic Act (“FFDCA”), and other federal and state statutes and regulations govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling and import and export of pharmaceutical products.

In the United States, biopharmaceutical products are subject to extensive regulation by the FDA under the Federal Food, Drug, and Cosmetic Act (“FFDCA”), the Public Health Service Act, and other federal and state statutes and regulations govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling and import and export of biopharmaceutical products.

Failure to comply with applicable U.S.

requirements may subject a company to a variety of administrative or judicial sanctions, such as clinical hold, FDA refusal to approve pending a New Drug Applications (“NDA”) warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties and criminal prosecution.

Our investigational medicines and any future investigational medicines must be approved by the FDA pursuant to an NDA before they may be legally marketed in the United States.

requirements may subject a company to a variety of administrative or judicial sanctions, such as clinical hold, FDA refusal to approve pending New Drug Applications (“NDAs”) or Biologic License Applications (“BLAs”), warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties and criminal prosecution.

Our investigational medicines and any future investigational medicines must be approved by the FDA before they may be legally marketed in the United States.

The process generally involves the following:

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• Performance of adequate and well-controlled human clinical trials in accordance with applicable Investigational New Drug (“IND”) regulations, Good Clinical Practice (“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;

• Payment of any user fees for FDA review of an NDA;

• A determination by the FDA within 60 days of its receipt of an NDA 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 components thereof, will be produced to assess compliance with Good Manufacturing Practices (“cGMP”) requirements to assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;

• Satisfactory completion of any potential FDA audits of the clinical trial sites that generated the data in support of the NDA to assure compliance with GCPs and integrity of the clinical data;

• FDA review and approval of an NDA, including consideration of the views of any FDA advisory committee;

• Submission to the FDA of an NDA for small molecule candidates and BLA for biologic candidates;

• Payment of any user fees for FDA review of applications;

• A determination by the FDA within 60 days of its receipt of an application to accept the filing for review;

• Satisfactory completion of any potential FDA audits of the clinical trial sites that generated the data in support of the application to assure compliance with GCPs and integrity of the clinical data;

• FDA review and approval of an NDA or BLA, including consideration of the views of any FDA advisory committee;

• Compliance with any post-approval requirements, including risk evaluation and mitigation strategy (“REMS”), where applicable, and post-approval studies required by the FDA as a condition of approval.

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Preclinical Studies

Before testing any drug product candidates in humans, the product candidate must undergo rigorous preclinical testing.

Before testing any product candidates in humans, the product candidate must undergo rigorous preclinical testing.

Preclinical tests include laboratory evaluation of product chemistry, formulation and toxicity, as well as in vitro and animal studies to assess the potential for adverse events and in some cases to establish a rationale for therapeutic use.

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Clinical Trials

Clinical trials involve the administration of the investigational new drug to healthy volunteers or patients under the supervision of a qualified investigator, generally a physician not employed by or under the trial sponsor’s control.

Clinical trials involve the administration of the investigational new drug or biologic to healthy volunteers or patients under the supervision of a qualified investigator, generally a physician not employed by or under the trial sponsor’s control.

Clinical trials must be conducted:

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If a foreign clinical trial is not conducted under an IND, the sponsor may submit data from the clinical trial to the FDA in support of an NDA.

The FDA will accept a well-designed and well-conducted foreign clinical

trial not conducted under an IND if the clinical trial was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

The FDA will accept a well-designed and well-conducted foreign clinical trial not conducted under an IND if the clinical trial was conducted in accordance with GCP requirements, and the FDA is able to validate the data through an onsite inspection if deemed necessary.

Clinical trials are generally conducted in three sequential phases, known as Phase 1, Phase 2 and Phase 3:

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This group provides authorization for whether a trial may move forward at designated checkpoints based on access to certain data from the trial.

Concurrent with clinical trials, companies usually complete additional animal studies and must develop additional information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

Concurrent with clinical trials, companies usually complete additional animal studies and must develop additional information about the chemistry and physical characteristics of the product as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of the product and, among other things, companies must develop methods for testing the identity, strength, quality, potency and purity of the final product.

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FDA Review Process

After completion of the required clinical testing, an NDA is prepared and submitted to the FDA.

FDA approval of an NDA is required before marketing of the product may begin in the U.S.

An NDA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls.

After completion of the required clinical testing, an NDA or BLA is prepared and submitted to the FDA.

FDA approval of an NDA or BLA is required before marketing of the product may begin in the U.S.

An NDA or BLA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls.

To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of the investigational product to the satisfaction of the FDA.

FDA approval of an NDA must be obtained before a drug may be marketed in the United States.

The cost of preparing and submitting an NDA is substantial.

Under the Prescription Drug User Fee Act (“PDUFA”), each NDA must be accompanied by a substantial user fee.

The FDA adjusts the PDUFA user fees on an annual basis.

FDA approval of an NDA or BLA must be obtained before a drug or biologic may be marketed in the United States.

Under the Prescription Drug User Fee Act (“PDUFA”), each NDA or BLA must be accompanied by a substantial user fee.

The FDA adjusts the user fees on an annual basis.

Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first application filed by a small business.

Additionally, no user fees are assessed on NDAs for products designated as orphan drugs, unless the product also includes a non-orphan indication.

The applicant under an approved NDA is also subject to an annual program fee.

The FDA reviews each submitted NDA before it determines whether to file it and may request additional information.

The FDA must make a decision on whether to file an NDA within 60 days of receipt, and such decision could include a refusal to file by the FDA.

Once the submission is filed, the FDA begins an in-depth review of an NDA.

The FDA has agreed to certain performance goals in the review of an NDA.

Most applications for standard review drug products are reviewed within ten to twelve months;

most applications for priority review drugs are reviewed in six to eight months.

Priority review can be applied to drugs that the FDA determines may offer significant improvement in safety or effectiveness compared to marketed products or where no adequate therapy exists.

Additionally, no user fees are assessed on applications for products designated as orphan drugs, unless the product also includes a non-orphan indication.

The sponsor under an approved application is also subject to an annual program fee.

The FDA reviews each submitted NDA or BLA before it determines whether to file it and may request additional information.

The FDA must make a decision on whether to file an application within 60 days of receipt, and such decision could include a refusal to file by the FDA.

Once the submission is filed, the FDA begins an in-depth review of the application.

The FDA has agreed to certain performance goals in the review process.

Most applications for standard review products are reviewed within ten months of filing;

most applications for priority review are reviewed in six months from filing.

Priority review can be applied to products that the FDA determines may offer significant improvement in safety or effectiveness compared to marketed products or where no adequate therapy exists.

The review process for both standard and priority review may be extended by the FDA for three additional months to consider certain late-submitted information, or information intended to clarify information already provided in the submission.

The FDA does not always meet its goal dates for standard and priority timeframes for an NDA, and the review process can be extended by FDA requests for additional information or clarification.

The FDA may also refer applications for novel drug products, or drug products that present difficult questions of safety or efficacy, to an outside advisory committee—typically a panel that includes clinicians and other experts—for review, evaluation and a recommendation as to whether the application should be approved and under what conditions, if any.

The FDA does not always meet its goal dates for standard and priority timeframes, and the review process can be extended by FDA requests for additional information or clarification.

The FDA may also refer applications for novel products, or products that present difficult questions of safety or efficacy, to an outside advisory committee—typically a panel that includes clinicians and other experts—for review, evaluation and a recommendation as to whether the application should be approved and under what conditions, if any.

The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.

Before approving an NDA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine whether they comply with cGMP requirements.

Before approving an NDA or BLA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine whether they comply with cGMP requirements.

The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

The FDA also typically inspects clinical trial sites to ensure compliance with GCP requirements and the integrity of the data supporting safety and efficacy.

After the FDA evaluates an NDA and the manufacturing facilities, it issues either an approval letter or a complete response letter.

After the FDA evaluates the application and the manufacturing facilities, it issues either an approval letter or a complete response letter.

A complete response letter (“CRL”), generally outlines the deficiencies in the submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application, such as additional clinical data, additional pivotal clinical trial(s), and/or other significant and time-consuming requirements related to clinical trials, preclinical studies or manufacturing.

If a CRL is issued, the applicant may resubmit an NDA addressing all of the deficiencies identified in the letter, withdraw the application, engage in formal dispute resolution or request an opportunity for a hearing.

If a CRL is issued, the applicant may resubmit the NDA or BLA addressing all of the deficiencies identified in the letter, withdraw the application, engage in formal dispute resolution or request an opportunity for a hearing.

The FDA has committed to reviewing resubmissions in two or six months depending on the type of information included.

Even if such data and information are submitted, the FDA may decide that an NDA does not satisfy the criteria for approval.

As a potential condition of an NDA approval, the FDA may require a REMS to help ensure that the benefits of the drug outweigh the potential risks to patients.

Even if such data and information are submitted, the FDA may decide that an application does not satisfy the criteria for approval.

As a potential condition of approval, the FDA may require a REMS to help ensure that the benefits of the product outweigh the potential risks to patients.

A REMS can include medication guides, communication plans for healthcare professionals and elements to assure a product’s safe use (“ETASU”).

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Moreover, the FDA may require substantial post-approval testing and surveillance to monitor the product’s safety or efficacy.

Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of an NDA supplement or, in some case, a new NDA, before the change can be implemented.

An NDA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDA supplements as it does in reviewing NDAs.

Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of an NDA or BLA supplement or, in some case, a new application, before the change can be implemented.

A supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing supplements as it does in reviewing NDAs and BLAs.

Orphan Drug Designation

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The FDA must determine if the drug candidate qualifies for fast track designation within 60 days of receipt of the sponsor’s request.

For fast track products, sponsors may have greater interactions with the FDA and the FDA may initiate review of sections of a fast track product’s NDA before the application is complete.

For fast track products, sponsors may have greater interactions with the FDA and the FDA may initiate review of sections of a fast track product’s NDA or BLA before the application is complete.

This rolling review is available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a fast track product may be effective.

The sponsor must also provide, and the FDA must approve, a schedule for the submission of the remaining information and the sponsor must pay applicable user fees.

At the time of an NDA filing, the FDA will determine whether to grant priority review designation.

At the time of an NDA or BLA filing, the FDA will determine whether to grant priority review designation.

Additionally, fast track designation may be withdrawn if the FDA believes that the designation is no longer supported by data emerging in the clinical trial process.

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Breakthrough therapy designation may be granted for products that are intended, alone or in combination with one or more other products, to treat a serious or life-threatening condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints.

Under the breakthrough therapy program, the sponsor of a new drug candidate may request that the FDA designate the candidate for a

specific indication as a breakthrough therapy concurrent with, or after, the submission of an IND for the drug candidate.

Under the breakthrough therapy program, the sponsor of a new drug candidate may request that the FDA designate the candidate for a specific indication as a breakthrough therapy concurrent with, or after, the submission of an IND for the drug candidate.

The FDA must determine if the drug product qualifies for breakthrough therapy designation within 60 days of receipt of the sponsor’s request.

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Pediatric Information

Under the Pediatric Research Equity Act (“PREA”), an NDA or supplements to an NDA must contain data to assess the safety and effectiveness of the drug for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the drug is safe and effective.

Under the Pediatric Research Equity Act (“PREA”), an NDA or BLA or supplements thereto must contain data to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

The FDA may grant full or partial waivers, or deferrals, for submission of data.

Unless otherwise required by regulation, PREA does not apply to any drug for an indication for which orphan designation has been granted, with certain exceptions.

The Best Pharmaceuticals for Children Act (“BPCA”) provides NDA holders a six-month extension of any exclusivity—patent or nonpatent—for a drug if certain conditions are met.

Conditions for exclusivity include the FDA’s determination that information relating to the use of a new drug in the pediatric population may produce health benefits in that population, the FDA

making a written request for pediatric studies, and the applicant agreeing to perform, and reporting on, the requested studies within the statutory timeframe.

Unless otherwise required by regulation, PREA does not apply to any product for an indication for which orphan designation has been granted, with certain exceptions.

The Best Pharmaceuticals for Children Act (“BPCA”) provides NDA or BLA holders a six-month extension of any exclusivity—patent or nonpatent—for a product if certain conditions are met.

Conditions for exclusivity include the FDA’s determination that information relating to the use of a new product in the pediatric population may produce health benefits in that population, the FDA making a written request for pediatric studies, and the applicant agreeing to perform, and reporting on, the requested studies within the statutory timeframe.

Applications under the BPCA are treated as priority applications, with all of the benefits that designation confers.

Post-Approval Requirements

Once an NDA is approved, a product will be subject to certain post-approval requirements.

For instance, the FDA closely regulates the post-approval marketing and promotion of drugs, including standards and regulations for direct-to-consumer advertising, off-label promotion, industry-sponsored scientific and educational activities and promotional activities involving the internet.

Drugs may be marketed only for the approved indications and in a manner consistent with the approved labeling.

Adverse event reporting and submission of periodic reports are required following FDA approval of an NDA.

The FDA also may require post-marketing testing, known as phase 4 testing, REMS, and surveillance to monitor the effects of an approved product, or the FDA may place conditions on an approval that could restrict the distribution or use of the product.

Once an NDA or BLA is approved, a product will be subject to certain post-approval requirements.

For instance, the FDA closely regulates the post-approval marketing and promotion of biopharmaceutical products, including standards and regulations for direct-to-consumer advertising, off-label promotion, industry-sponsored scientific and educational activities and promotional activities involving the internet.

Products may be marketed only for the approved indications and in a manner consistent with the approved labeling.

Adverse event reporting and submission of periodic reports are required following FDA approval of an NDA or BLA.

The FDA also may require post-marketing testing, known as phase 4 testing, REMS, and surveillance to monitor the effects of an approved

product, or the FDA may place conditions on an approval that could restrict the distribution or use of the product.

In addition, quality control, drug manufacture, packaging and labeling procedures must continue to conform to cGMP after approval.

Drug manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies.

Manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies.

Registration with the FDA subjects entities to periodic unannounced inspections by the FDA, during which the Agency inspects manufacturing facilities to assess compliance with cGMP.

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• Fines, warning or other enforcement-related letters or holds on post-approval clinical studies;

• Refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals;

• Refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals;

• Product seizure or detention, or refusal to permit the import or export of products;

• Injunctions or the imposition of civil or criminal penalties.

The Hatch-Waxman Act Orange Book Listing

Under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch Waxman Amendments, NDA applicants are required to identify to the FDA each patent whose claims cover the applicant’s drug or approved method of using the drug.

Upon approval of a drug, the applicant must update its listing of patents to the NDA in timely fashion and each of the patents listed in the application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book.

Drugs listed in the Orange Book can, in turn, be cited by potential generic competitors in support of approval of an abbreviated new drug application (“ANDA”).

An ANDA provides for marketing of a drug product that has the same active ingredient(s),

strength, route of administration, and dosage form as the listed drug and has been shown through bioequivalence testing to be therapeutically equivalent to the listed drug.

An approved ANDA product is considered to be therapeutically equivalent to the listed drug.

Other than the requirement for bioequivalence testing, ANDA applicants are not required to conduct, or submit results of, pre-clinical or clinical tests to prove the safety or effectiveness of their drug product.

Drugs approved under the ANDA pathway are commonly referred to as “generic equivalents” to the listed drug and can often be substituted by pharmacists under prescriptions written for the original listed drug pursuant to each state’s laws on drug substitution.

The ANDA applicant is required to certify to the FDA concerning any patents identified for the reference listed drug in the Orange Book.

Specifically, the applicant must certify to each patent in one of the following ways:

(i) the required patent information has not been filed;

(ii) the listed patent has expired;

(iii) the listed patent has not expired but will expire on a particular date and approval is sought after patent expiration;

or (iv) the listed patent is invalid or will not be infringed by the new product.

A certification that the new product will not infringe the already approved product’s listed patents, or that such patents are invalid, is called a Paragraph IV certification.

For patents listed that claim an approved method of use, under certain circumstances the ANDA applicant may also elect to submit a section viii statement certifying that its proposed ANDA label does not contain (or carves out) any language regarding the patented method-of-use rather than certify to a listed method-of-use patent.

If the applicant does not challenge the listed patents through a Paragraph IV certification, the ANDA application will not be approved until all the listed patents claiming the referenced product have expired.

If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA-holder and patentee(s) once the ANDA has been accepted for filing by the FDA (referred to as the “notice letter”).

The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice letter.

The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months from the date the notice letter is received, expiration of the patent, the date of a settlement order or consent decree signed and entered by the court stating that the patent that is the subject of the certification is invalid or not infringed, or a decision in the patent case that is favorable to the ANDA applicant.

The ANDA application also will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired.

In some instances, an ANDA applicant may receive approval prior to expiration of certain non-patent exclusivity if the applicant seeks, and the FDA permits, the omission of such exclusivity-protected information from the ANDA prescribing information.

Upon an NDA approval of a new chemical entity (“NCE”), which is a drug that contains no active moiety that has been approved by the FDA in any other NDA, that drug receives five years of marketing exclusivity during which the FDA cannot receive any ANDA seeking approval of a generic version of that drug unless the application contains a Paragraph IV certification, in which case the application may be submitted one year prior to expiration of the NCE exclusivity.

If there is no listed patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no ANDA for a generic version of the drug may be filed before the expiration of the exclusivity period.

Certain changes to an approved drug, such as the approval of a new indication, the approval of a new strength, and the approval of a new condition of use, are associated with a three-year period of exclusivity from the date of approval during which the FDA cannot approve an ANDA for a generic drug that includes the change.

In some instances, an ANDA applicant may receive approval prior to expiration of the three-year exclusivity if the applicant seeks, and the FDA permits, the omission of such exclusivity-protected information from the ANDA package insert.

Patent Term Extension

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Patent term extension, however, cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.

After an NDA approval, owners of relevant drug patents may apply for the extension.

The allowable patent term extension is calculated as half of the drug’s testing phase (the time between an IND application and an NDA

submission) and all of the review phase (the time between an NDA submission and approval) up to a maximum of five years.

After approval, owners of relevant patents may apply for the extension.

The allowable patent term extension is calculated as half of the product’s testing phase (the time between an IND application and an NDA or BLA submission) and all of the review phase (the time between NDA or BLA submission and approval) up to a maximum of five years.

The time can be reduced for any time the FDA determines that the applicant did not pursue approval with due diligence.

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The director of the USPTO must determine that approval of the drug covered by the patent for which a patent extension is being sought is likely.

Interim patent extensions are not available for a drug for which an NDA has not been submitted.

Coverage, Pricing, and Reimbursement

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Third-party payors may limit coverage to specific product candidates on an approved list, known as a formulary, which might not include all FDA-approved drugs for a particular indication.

Further, HHS imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis.

HHS has also been empowered to negotiate the price of certain single-source drugs that have been on the market for at least seven (7) years and biologics that have been on the market for at least eleven (11) years covered under Medicare as part of the Medicare Drug Price Negotiation Program.

Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program.

Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

Outside the United States, the commercialization of therapeutics is generally subject to extensive governmental price controls and other market regulations, and we believe the increasing emphasis on cost containment initiatives in Europe, Canada and other countries has, and will continue to, put pressure on the pricing and usage of therapeutics such as our product candidates.

Other Healthcare Laws

In addition to FDA restrictions on marketing of pharmaceutical products, several other types of state and federal laws have been applied to restrict certain general business and marketing practices in the pharmaceutical industry in recent years.

These laws include anti-kickback statutes, false claims statutes and other healthcare laws and regulations.

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This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers, among others, on the other.

Although there are a number of statutory exceptions and regulatory safe harbors protecting certain common activities from prosecution or other regulatory sanctions, the exceptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor.

drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor.

In addition, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to commit a violation.

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Most states also have statutes or regulations similar to the federal Anti-Kickback Statute and civil False Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

Other federal statutes pertaining to healthcare fraud and abuse include the civil monetary penalties statute, which prohibits, among other things, the offer or payment of remuneration to a Medicaid or Medicare beneficiary that the offerer or payor knows or should know is likely to influence the beneficiary to order a receive a reimbursable item or service from a particular supplier, and the additional federal criminal statutes created by the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which prohibits, among other things, knowingly and willfully executing or attempting to execute a scheme to defraud any healthcare benefit program or obtain by means of false or fraudulent pretenses, representations or promises any money or property owned by or under the control of any healthcare benefit program in connection with the delivery of or payment for healthcare benefits, items or services.

Other federal statutes pertaining to healthcare fraud and abuse include the civil monetary penalties statute, which prohibits, among other things, the offer or payment of remuneration to a Medicaid or Medicare beneficiary that the offeror or payor knows or should know is likely to influence the beneficiary to order a receive a reimbursable item or service from a particular supplier, and the additional federal criminal statutes created by the Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), which prohibits, among other things, knowingly and willfully executing or attempting to execute a scheme to defraud any healthcare benefit program or obtain by means of false or fraudulent pretenses, representations or promises any money or property owned by or under the control of any healthcare benefit program in connection with the delivery of or payment for healthcare benefits, items or services.

Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to commit a violation.

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Some states require the reporting of certain drug pricing information, including information pertaining to and justifying price increases.

In addition, states such as California, Connecticut, Nevada and Massachusetts require pharmaceutical companies to implement compliance programs and/or marketing codes.

Several additional states are considering similar proposals.

Certain states and local jurisdictions also require the registration of pharmaceutical sales and medical representatives.

Compliance with these laws is difficult and time consuming, and companies that do not comply with these state laws face civil penalties.

In addition, certain states require pharmaceutical companies to implement compliance programs and/or marketing codes.

Certain states and local jurisdictions also require certain regulatory licenses to manufacture or distribute products commercially and/or the registration of pharmaceutical sales and medical representatives.

Compliance with these laws is difficult and time consuming, and companies that do not comply with these state laws may face significant penalties.

Efforts to ensure that business arrangements with third parties comply with applicable healthcare laws and regulations involve substantial costs.

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The pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.

For example, in March 2010, the ACA was enacted, which intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms, substantially changed the way healthcare is financed by both governmental and private insurers, and significantly impacts the U.S.

pharmaceutical industry.

There have been judicial, executive brand, and Congressional challenges and amendments to certain aspects of the ACA, For example, 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 ACA 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 creating a new manufacturer discount program.

However, it is possible that the ACA will be subject to judicial or Congressional challenges in the future.

It is unclear how such challenges will impact the ACA.

Tempest cannot predict the ultimate content, timing or effect of any healthcare reform legislation or the impact of potential legislation on its business.

For example, in March 2010, the ACA was enacted, substantially changed the way healthcare is financed by both governmental and private insurers.

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

For example, on July 4, 2025, the One Big Beautiful Bill Act the (“OBBBA”) was signed into law, which narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies.

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

On August 2, 2011, the Budget Control Act of 2011, was enacted which, among other things, included aggregate reductions of Medicare payments to providers of 2% per fiscal year.

These reductions went into effect on April 1, 2013 and, due to subsequent legislative amendments to the statute will remain in effect through 2032, unless additional Congressional action is taken.

Recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products.

For example, the IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs covered under

Medicare that have been on the market for at least seven years, and subject drug manufacturers to civil monetary penalties and a potential excise tax by offering a price that is not equal to or less than the negotiated “maximum fair price” for such drugs and biologics under the law (the “Medicare Drug Price Negotiation Program”), and (ii) imposes rebates with respect to certain drugs and biologics covered under Medicare Part B or Medicare Part D to penalize price increases that outpace inflation.

The IRA permits HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

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

On August 15, 2024, HHS announced the agreed-upon price 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 2025.

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

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

These changes include aggregate reductions to Medicare payments to providers of 2% per fiscal year, which began in 2013 and will remain in effect until 2032 unless additional Congressional action is taken.

The current administration is pursuing policies to reduce regulations and expenditures across government agencies 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, for example, include directives to reduce agency workforce, rescinding an executive order tasking the Center for Medicare and Medicaid Innovation (“CMMI”) 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 AI task force and developing a strategic plan.

Further, amounts allocated to federal grants and contracts may be reduced or eliminated.

These reductions may also impact the ability of relevant agencies to timely review and approve research and development, manufacturing, and marketing activities, which may delay our ability to develop, market and sell any products we may develop.

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

Raimondo (“Loper Bright”), 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.

At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological 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.

Additionally, on May 30, 2018, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017 was signed into law.

The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a phase 1 clinical trial and that are undergoing investigation for FDA approval.

Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA authorization under an FDA expanded access program;

however, manufacturers are not obligated to provide investigational new drug products under the current federal right to try law.

For example, the current administration has announced agreements with several pharmaceutical companies that require the drug manufacturers to offer, through a direct to consumer platform (“TrumpRx”) U.S.

patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues.

Other recent actions, for example, include (1) directing agencies to reduce agency workforce and cut programs;

(2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives;

(3) imposing tariffs on imported pharmaceutical products;

and (4) as part of the Make America Healthy Again Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising.

Additionally, the current administration recently called on Congress to enact "The Great Healthcare Plan," to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager (“PBM”) payment methodologies, among other things.

These actions and policies may significantly reduce U.S.

drug prices, potentially impacting manufacturers’ global pricing strategies and profitability, while increasing their operational costs and compliance risks.

In June 2024, the U.S.

Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

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.

At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological 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.

Employees and Human Capital Resources

As of December 31, 2024, we had 25 employees, including 24 full-time employees and 18 holding Ph.D., M.D., JD, LL.M., MBA and/or M.S.

Our employees have established internal expertise in chemistry, biochemistry, molecular biology, immunology, pharmacology, toxicology, pre-clinical development, regulatory and quality, translational medicine, and early-to-late-stage clinical development, as well as finance, business development and strategic transactions.

As of March 1, 2026, we had four employees, including four full-time employees and three holding Ph.D., MBA and/or M.S.

Our employees have established internal expertise in cellular biology, pre-clinical development, and early-to-late-stage clinical development, as well as finance, business development and strategic transactions.

None of our employees are represented by a labor union or covered by collective bargaining agreements.

We will continue to add experienced and talented scientists in areas, such as medicinal chemistry, that we believe are critical for the discovery of highly differentiated small-molecule compounds.

We consider a number of measures and objectives in managing our human capital assets, including, among others, employee engagement, development and training, talent acquisition and retention, employee safety and wellness, diversity and inclusion,

and compensation and pay equity.

We provide our employees with salaries and bonuses intended to be competitive for our industry, opportunities for equity ownership, development programs that enable continued learning and growth and a benefits package to promote well-being across all aspects of their lives, including health care, retirement planning and paid time off.

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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