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Item 1. Business

2026-03-05 compared with 2025-02-27 · 147 added, 250 removed, 577 unchanged (41% of the section changed)

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These include modulation of the microvasculature via angiogenesis-targeted agents, induction of a potent immune response via activators on effector cells in the tumor microenvironment, and alleviation of immunosuppressive mechanisms used by tumors to evade immune surveillance.

We plan to advance our product candidates through clinical development as both standalone therapies and in combination with proprietary pipeline antibodies based on supportive clinical and nonclinical data.

Our pipeline comprises three clinical product candidates and one candidate in investigational new drug application (“IND”) enabling studies.

We plan to advance our product candidates through clinical development and commercialization as both standalone therapies and in combination with proprietary pipeline antibodies based on supportive clinical and nonclinical data.

Our pipeline consists of four clinical product candidates.

Our lead product candidate, tovecimig (formerly known as CTX-009), is a bispecific antibody targeting Delta-like ligand 4 (“DLL4”), a ligand of Notch-1, and vascular endothelial growth factor A (“VEGF-A”).

Simultaneous blockade of the VEGF-A and the Notch pathways is known to turn productive angiogenesis into non-productive angiogenesis, which leads to tumor shrinkage and apoptosis.

Our second program CTX-471, is an agonistic antibody targeting a member of the tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD-137, a co-stimulatory receptor which is mostly expressed on activated, but not on resting, T-cells and NK cells.

Our second program, CTX-471, is an agonistic antibody targeting a member of the tumor necrosis factor receptor superfamily member 9 (TNFRSF9), also known as CD-137 or 4-1BB, a co-stimulatory receptor which is mostly expressed on activated, but not on resting, T-cells and NK cells.

Our third program, CTX-8371, is a bispecific antibody targeting the programmed cell death protein-1 (“PD-1”), an inhibitory immune checkpoint receptor, and its ligand PD-L1, two validated immune-oncology targets.

In addition, we are in the process of IND enabling studies with CTX-10726, a bispecific antibody targeting PD-1 and VEFG-A.

Our fourth program, CTX-10726, is a bispecific antibody targeting PD-1 and VEFG-A.

Tovecimig (CTX-009), our bispecific antibody targeting DLL4 and VEGF-A, is currently being evaluated in a randomized Phase 2/3 trial in the United States in combination with paclitaxel in patients with biliary tract cancer (“BTC”) who received one prior treatment regimen.

We expect top-line data from this study at the end of the first quarter of 2025.

In August 2024, we also announced that tovecimig demonstrated a 5% overall response rate (“ORR”) as a monotherapy in our Phase 2 study of patients with advanced, metastatic colorectal cancer (“CRC”).

The two initial indications of BTC and CRC for tovecimig were selected based on the results of the Phase 1,1b and 2 clinical trials and the significant unmet need for effective therapeutic regimens in these patient populations.

We estimate that there are approximately 23,000 patients diagnosed with BTC in the United States each year and over 200,000 patients worldwide.

Patients with BTC have a poor prognosis despite first-line treatment with chemotherapy and immunotherapy, and there is no generally accepted standard of care in later lines of treatment, except for therapies for targeted mutations, which is estimated to be approximately 15% of the market.

For CRC, there are approximately 153,000 new patients diagnosed each year in the United States and more than 1.9 million patients worldwide.

Despite advances in treatment of CRC in recent years with angiogenesis inhibitors and targeted therapies, there are few safe and effective treatment options for patients with CRC, and the majority of the patients are refractory to existing therapeutic regimens or relapse quickly and advance to later lines of therapy where treatment options are more limited and less effective.

We also intend to expand the development of tovecimig to additional indications with significant unmet need such as ovarian cancer and gastric cancer.

The trial met its primary endpoint with an overall response rate (“ORR”) of 17.1% for tovecimig in combination with paclitaxel, including one complete response, compared to a 5.3% ORR for paclitaxel alone.

This difference was statistically significant with p=0.031.

In the Phase 2/3 trial, the prespecified event threshold of 80% overall survival (OS) events was reached in Q1 2026;

therefore, the analyses of progression-free survival (PFS) and OS are expected to be reported in April 2026.

Further, an ongoing Investigator Sponsored Trial (“IST”) is evaluating tovecimig in the front-line setting for patients with BTC, combining tovecimig with the standard first-line regimen of gemcitabine, cisplatin, and durvalumab.

We estimate that there are approximately 26,500 patients newly diagnosed with BTC in the United States each year and over 200,000 patients worldwide.

Patients with BTC have a poor prognosis despite first-line treatment with chemotherapy and immunotherapy, and there is no generally accepted standard of care in later lines of treatment, except for therapies addressing targeted mutations, which is estimated to be approximately 15% to 20% of the patient population.

Beyond BTC, we intend to expand the development of tovecimig to additional solid tumor indications with significant unmet need and a mechanistic rationale for using an angiogenic inhibitor, such as colorectal cancer (“CRC”), ovarian cancer, gastric cancer, renal cell carcinoma, and hepatocellular carcinoma.

In CRC, we presented data in January 2026 showing tovecimig demonstrated a 5% overall response rate (“ORR”) as a monotherapy in our Phase 2 study of patients with advanced, metastatic CRC treated in the third- and fourth-line settings.

Following the generation of positive clinical data in later lines of therapy, we plan to study tovecimig in earlier settings in all indications where the data support it.

CTX-471, our CD137 agonistic antibody, targets a key node of the immune system with the goal of becoming a next generation immune-oncology treatment for patients across a variety of cancers who do not have a sustained response to current therapies.

CTX-471, our CD137 (or 4-1BB) agonistic antibody, targets a key node of the immune system with the goal of becoming a next generation immune-oncology treatment for patients across a variety of cancers who do not have a sustained response to current therapies.

During its early clinical development, CTX-471 demonstrated monotherapy activity in the post-PD-1/PD-L1 patient population across three solid tumor indications:

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CTX-8371, our bispecific antibody targeting PD-1 and PD-L1, is currently in a first-in-human Phase 1 clinical trial.

In the dose escalation portion of the trial, CTX-8371 demonstrated deep responses in patients with three different tumor types;

non-small cell lung cancer (“NSCLC”), triple-negative breast cancer (“TNBC”) and Hodgkin lymphoma (“HL”), with no dose limiting toxicities observed.

We have initiated cohort expansions in patients with NSCLC and TNBC and expect a further expansion cohort in patients with HL to begin shortly.

CTX-8371 emerged from an unbiased screen for synergy conducted with our StitchMabs TM platform.

We subsequently tested CTX-8371 in several in vitro and in vivo models where it demonstrated enhanced activation of immune responses when compared with commercially available checkpoint blockers.

We subsequently tested CTX-8371 in several in vitro and in vivo models where it demonstrated enhanced activation of immune responses when compared with commercially available checkpoint blockers, which target either PD-1 or PD-L1, but not both.

We believe that CTX-8371 has the potential to become a next generation checkpoint inhibitor with improved activity across various solid tumors relative to approved checkpoint blockers.

We expect to complete our Phase 1 study of CTX-8371 in the second half of 2025.

Finally, CTX-10726, our bispecific antibody targeting PD-1 and VEGF-A, is currently in IND enabling studies, with an IND filing expected by year end 2025.

CTX-10726 is a fully human IgG1 with silenced Fc-γ receptor binding that was discovered and developed in-house.

We expect to accelerate the development of CTX-10726 by leveraging our experience developing and manufacturing bispecific structures containing VEGF-A (tovecimig) and PD-1 (CTX-8371) components.

The figure below details our pipeline of product candidates.

Finally, CTX-10726, our bispecific antibody targeting PD-1 and VEGF-A, is a fully human IgG1 with silenced Fc-γ receptor binding that was discovered and developed in-house.

In early 2026, we received FDA clearance for the IND for CTX-10726 and initiated a Phase 1 dose escalation study.

We expect to accelerate the development of CTX-10726 by leveraging our experience developing and manufacturing bispecific structures containing the VEGF-A and PD-1 components.

Our scientific focus is on the relationship between angiogenesis, the immune system, and tumor growth.

Our pipeline of novel product candidates is designed to target multiple critical biological pathways required for an effective anti-tumor response.

Our strategy to achieve this goal includes:

Advance our product candidate, tovecimig (DLL4 x VEGF-A bispecific antibody), through clinical development and potential commercialization for multiple indications .

Tovecimig is an investigational bispecific antibody that simultaneously blocks the DLL4 and VEGF-A signaling pathways, which are critical to angiogenesis and tumor vascularization.

We chose BTC and CRC as our first indications based on a number of factors, including tovecimig’s activity observed in the Phase 1, 1b and 2 clinical trials and the lack of effective therapies for these patient populations.

We completed enrollment of a randomized Phase 2/3 trial of tovecimig in combination with paclitaxel in patients with BTC and a Phase 2 trial of tovecimig in patients with advanced CRC.

In addition, an investigator sponsored trial of tovecimig in the first-line setting in combination with gemcitabine/cisplatin and durvalumab in patients with BTC was initiated in the first quarter of 2025.

We intend to explore the potential of tovecimig in other indications where the data support its potential therapeutic benefit such as ovarian cancer, gastric cancer, renal cell cancer, and liver cancer.

Advance our product candidate, CTX-471 (CD137 agonist antibody), through clinical development to evaluate its therapeutic potential and define a regulatory pathway for approval.

We seek to translate the antitumor activity of CTX-471 observed in preclinical testing and in our Phase 1 trial into meaningful clinical results in patients with solid tumors, such as SCLC, non-small cell lung cancer (“NSCLC”) and melanoma.

Our Phase 1a clinical trial was conducted in patients who relapsed or progressed after at least three months of a prior checkpoint therapy.

As of January 31, 2025, two patients remain on trial.

During the Phase 1a trial, we identified a potential biomarker of activity, neural cell adhesion molecule (NCAM or CD56), which we intend to use in a Phase 2 basket study of CTX-471, expected to start in mid-2025.

Advance CTX-8371 (PD-1 x PD-L1 bispecific antibody) through clinical development as a next generation checkpoint inhibitor.

CTX-8371 has demonstrated better antitumor activity in preclinical experiments than a single PD-1, a single PD-L1, or combinations of PD-1 and PD-L1 inhibitors.

We initiated a first-in-human Phase 1 clinical trial with the first patient dosed in April 2024.

As of January 2025, the third cohort of this trial completed with no dose limiting toxicities observed.

Advance CTX-10726 (PD-1 x VEFG-A bispecific antibody) through IND-enabling studies and clinical development.

CTX-10726 was developed at Compass leveraging our experience with the VEGF-A component of tovecimig and the PD-1 component of CTX-8371.

We are currently performing IND enabling studies and anticipate filing an IND by year end 2025.

Seek strategic partnerships for select product candidates.

Our technology platform is designed to generate a broad pipeline of product candidates with high potential for clinical application.

Our strategy to achieve this goal includes advancing our product candidates through clinical development and commercialization.

This may include combining our product candidates with other drugs or with each other through various indications and lines of therapy.

We may also seek strategic partnerships for select product candidates.

Our research and discovery platform is designed to generate a broad pipeline of product candidates with high potential for clinical application.

We intend to assess on a case-by-case basis the opportunities for accelerating the preclinical development, clinical development and commercialization of these candidates in a capital-efficient manner, including selectively pursuing strategic partnerships with leading biopharmaceutical companies with domain-specific clinical development and commercial expertise to maximize the value of our pipeline.

The figure below details our pipeline of product candidates.

Product Candidates

We currently have three product candidates in the clinical stage of development:

tovecimig, CTX-471 and CTX-8371.

Additionally, we have one product candidate in IND enabling studies, CTX-10726.

We currently have four product candidates in the clinical stage of development:

tovecimig, CTX-471, CTX-8371, and CTX-10726.

In addition, we are developing multiple additional product candidates.

Tovecimig (DLL4 X VEGF-A bispecific antibody)

Tovecimig (formerly known as CTX-009) is an investigational bispecific antibody that is designed to simultaneously block the DLL4 and VEGF-A signaling pathways, which are critical to angiogenesis and tumor vascularization.

Preclinical and early clinical data of tovecimig as a monotherapy and in combination with chemotherapy suggest that blockade of both pathways provides robust anti-tumor activity across several solid tumor indications, including colorectal, gastric, cholangiocarcinoma, pancreatic and NSCLC.

Preclinical and early clinical data of tovecimig as a monotherapy and in combination with chemotherapy suggest that blockade of both pathways provides robust anti-tumor activity across several solid tumor indications, including cholangiocarcinoma, colorectal cancer, gastric cancer, pancreatic cancer, and NSCLC.

Tovecimig is undergoing clinical development in patients with advanced solid tumors in the United States.

A Phase 1 dose escalation and dose expansion monotherapy trial in patients with solid tumors, a Phase 1b trial of tovecimig in combination with chemotherapy and a Phase 2 trial of tovecimig in combination with chemotherapy in patients with advanced biliary tract cancer were completed in South Korea.

Data from the Phase 2 trial were presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (“ASCO GI”) in January 2023.

We are currently conducting a randomized Phase 2/3 trial of tovecimig in combination with paclitaxel in patients with advanced BTC.

Previously, tovecimig underwent a Phase 1 dose escalation and dose expansion monotherapy trial in patients with solid tumors, a Phase 1b trial in combination with chemotherapy, and a Phase 2 trial in combination with chemotherapy in patients with advanced biliary tract cancer, all of which were completed in South Korea.

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South Korean rights are held by Handok Pharmaceuticals, Inc.

(“Handok”) and China rights were out-licensed from us to Elpiscience Biopharmaceuticals Co., Limited (“Elpiscience”).

Phase 1 Summary of Clinical Activity of Tovecimig at the Recommended Phase 2 Dose ( RP2D ) – South Korea

The observed ORR of tovecimig at the 10 and 12.5 mg/kg doses were 18.8% (3/16) as a monotherapy and 23.5% (4/17) in combination with chemotherapy.

The clinical benefit rate (“CBR”) of tovecimig at the 10 and 12.5 mg/kg were 68.8% (11/16) as a monotherapy and 76.5% (13/17) in combination with chemotherapy.

In October 2021, we, along with ABL Bio, presented clinical trial data from the tovecimig Phase 1a/1b dose escalation and dose expansion trial at a plenary oral session during the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Abstract Number:

Session title:

Plenary Session 2:

New Drugs on the Horizon I).

The significant findings presented were as follows:

Tovecimig was generally well-tolerated and demonstrated single agent activity in heavily pre-treated patients with solid tumors who were resistant to anti-VEGF therapies, mostly of colorectal and gastric origins

The maximum tolerated dose (“MTD”) was not reached, and the RP2D of tovecimig were determined to be 10.0 and 12.5 mg/kg biweekly

ORR of tovecimig as a monotherapy across all doses tested (0.3 – 17.5 mg/kg) was 8% and the CBR was 62% in patients treated at the 3rd and 4th line settings

Treatment with tovecimig as a monotherapy at the RP2D (10.0 mg/kg and 12.5 mg/kg) led to 18.8% (n=3/16) ORR, not including an additional unconfirmed PR, and a 68.5% CBR (n=11/16)

Phase 2 Trial of Tovecimig with Paclitaxel in BTC - South Korea

(“Handok”) and China rights were out-licensed to Elpiscience Biopharmaceuticals Co., Limited (“Elpiscience”).

Phase 1b and 2 Trials of Tovecimig with Paclitaxel in Patients with BTC - South Korea

In the Phase 1b study, there were four patients enrolled with cholangiocarcinoma.

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Both of these patients received tovecimig in combination with paclitaxel.

Based on this observation, a Phase 2 trial of tovecimig in combination with paclitaxel was completed by ABL Bio in patients with BTC, with data reported in the first quarter of 2023.

Based on this observation, a Phase 2 trial of tovecimig in combination with paclitaxel was completed by Handok and Compass in patients with BTC, with data reported in the first quarter of 2023.

The trial enrolled patients with unresectable advanced, metastatic, or relapsed BTC who had received one or two prior systemic therapies.

This Phase 2 trial utilized a Simon Two-Stage adaptive design where the criteria to advance to the second stage of the trial was three PRs observed in 21 evaluable patients.

In the preliminary analysis of all 24 patients participating in the study, tovecimig with paclitaxel demonstrated a 37.5% ORR based on 9 patients with PRs that were confirmed by RECIST 1.1.

In the preliminary analysis of 24 patients participating in the study, tovecimig with paclitaxel demonstrated a 37.5% ORR based on 9 patients with PRs that were confirmed by RECIST 1.1.

The results of Part 1 of the Phase 2 trial were presented at the 2023 ASCO GI meeting in January 2023.

Based on the efficacy data and following discussions with the U.S.

Food and Drug Administration (“FDA”), while the trial had met the criteria to advance to Part 2, we elected to terminate the study and advance tovecimig directly to a randomized Phase 2/3 study in patients with BTC treated in the second-line setting.

Based on the efficacy data and following discussions with the FDA, while the trial had met the criteria to advance to Part 2, FDA recommended and we agreed to forego the second stage of the study and advance tovecimig directly to a randomized Phase 2/3 study in patients with BTC treated in the second-line setting.

Safety Data Summary

Tovecimig safety data has been analyzed and was observed to be generally well-tolerated.

Of the 24 patients enrolled in the first stage of the trial, all patients had at least one treatment emergent adverse event (“TEAE”).

Of the 24 patients enrolled in the trial, all patients had at least one treatment emergent adverse event (“TEAE”).

Grade 3 or greater TEAEs were reported in 95.8% of patients regardless of the relationship to tovecimig or paclitaxel, including decreased neutrophil count (83.3%), hypertension (16.7%), anemia (20.8%), and decreased platelet count (12.5%).

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The first stage of the trial enrolled 24 patients and 22 of those patients were considered evaluable.

Nine PRs confirmed by RECIST 1.1 were observed leading to an ORR of 37.5%, and 22 of the 24 patients evaluated have had stable disease or better with a decline in tumor burden leading to a CBR of 92%.

PRs were observed in all four tumor sub-types types (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma).

Of the 24 patients, 11 were treated in the second line with 7 PRs observed, leading to an ORR of 63.6% in this sub-group.

In the third line, 13 patients were treated with 2 PRs observed, leading to an ORR of 15.4% in the second sub-group.

After a median follow up of approximately 12 months, the median progression free survival (“PFS”) was 9.4 months, median duration of response (“DOR”) was 6.9 months and median overall survival (“OS”) was 12.5 months.

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FOLFOX demonstrated an ORR of 4.9%, a median PFS of 4.0 months, and a median OS of 6.2 months in a randomized study against best supportive care.

The waterfall plot below depicts the best response for the 22 patients evaluated in the trial.

The waterfall plot below depicts the best response for the 22 patients evaluable in the trial.

tovecimig + paclitaxel in BTC

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A schema of the trial design is provided below:

The trial was designed to enroll 150 patients, randomized in a 2:1 ratio to receive tovecimig plus paclitaxel (n=100) or paclitaxel alone (n=50).

The primary endpoint of the trial is ORR and the secondary endpoints include PFS, OS, DOR and DCR among others.

Patients who were randomized to receive paclitaxel and have progressed on their regimen can cross over to the tovecimig plus paclitaxel arm after progression on paclitaxel if they still meet the enrollment criteria for the study.

The trial was fully enrolled in August 2024 with 168 patients randomized in a 2:1 ratio to receive tovecimig plus paclitaxel (n=111) or paclitaxel alone (n=57).

The primary endpoint of the trial was ORR and the secondary endpoints include PFS, OS, and DOR.

Patients who were randomized to receive paclitaxel and progressed on their regimen could cross over to the tovecimig plus paclitaxel arm after progression on paclitaxel if they still met the enrollment criteria for the study.

To adjust for this treatment crossover, OS will be evaluated using the rank preserving structural failure time (“RPSFT”) method, as well as on an intent-to-treat basis.

A detailed description of the trial can be found on www.clinicaltrials.gov (Identifier NCT 05506943).

This trial was fully enrolled in August 2024.

Top line data is expected at the end of the first quarter of 2025.

In April 2025, we announced that the trial met its primary endpoint of ORR with a response rate of 17.1% for tovecimig in combination with paclitaxel, including one complete response, compared to 5.3% ORR for paclitaxel alone, with a p-value of 0.031.

The waterfall plot below depicts the best overall response for patients evaluated in the trial.

We expect to report additional top-line data from this study in April 2026, including progression-free survival and overall survival.

Phase 2 Trial of Tovecimig in CRC – United States

We conducted a Phase 2 monotherapy clinical trial of tovecimig in patients with metastatic colorectal cancer who have received two or three prior systemic therapies.

This trial was designed to assess the safety and efficacy of tovecimig as a monotherapy in patients with advanced CRC.

The trial utilized a Simon Two-Stage adaptive design where the criteria to advance to the second stage of the trial was three PRs observed in 37 patients enrolled in Stage 1 of the trial.

The first stage of the trial enrolled 41 patients in the United States, of which 26 (63%) were treated in the fourth line.

Tovecimig demonstrated an ORR of 5% (2 out of 41), a DCR of 71% (29 out of 41), median PFS of 3.9 months and median overall survival (“OS”) of 10.2 months.

The safety profile was consistent with the prior clinical trials with hypertension as the most common adverse event.

The ORR did not meet the criteria to advance to the second stage of the trial, but based on this efficacy signal we are planning to initiate a new second-line trial of tovecimig.

We are evaluating the details of this study to investigate tovecimig in combination with chemotherapy in patients with metastatic CRC based on DLL4 positivity and expect to initiate it in mid-2025.

Additional Plans for Tovecimig

We intend to explore the potential of tovecimig in additional indications, based on data from pre-clinical models, potential biomarkers such as DLL4, and clinical data from tovecimig trials providing signs of potential activity of tovecimig in additional indications such as ovarian cancer, gastric cancer,, renal cell cancer, and liver cancer.

In addition, we are developing a plan to study the combination of tovecimig with our novel bispecific checkpoint blocker, CTX-8371, and with other checkpoint blockers, such as pembrolizumab and atezolizumab.

Additionally, we are considering the combination of tovecimig with our novel CD137 agonistic antibody, CTX-471.

CTX-471 (CD137 agonist antibody)

In January 2026, we presented data at ASCO GI from tovecimig’s Phase 2 monotherapy study in patients with advanced, metastatic CRC treated in the third- and fourth-line settings.

Tovecimig demonstrated monotherapy activity, with an overall response rate of 5% (2 out of 40 patients), in heavily pre-treated patients, all of whom had previously been treated with bevacizumab (~51% had been treated with two or more prior rounds of bevacizumab).

Tovecimig also demonstrated a DCR of 68% (27 out of 40), median PFS of 3.9 months and median OS of 10.2 months.

Although DLL4 expression on colorectal tumors is a negative prognostic factor, the data indicate that patients with DLL4-positive tumors did better with tovecimig therapy than patients with DLL4-negative tumors.

Tovecimig’s safety profile was generally consistent with prior studies with hypertension as the most common treatment-emergent adverse event, all of which occurred in patients with a prior history of hypertension.

Additional Development Plans for Tovecimig

We are preparing for a Phase 2 basket study of tovecimig in a broader set of patients with DLL4+ cancers, potentially including gastric, ovarian, renal, hepatocellular, and colorectal cancers.

We expect to initiate the study mid-2026 following a comprehensive analysis of the complete data set from the COMPANION-002 BTC trial.

In addition, we are developing a plan to study the combination of tovecimig with our novel bispecific checkpoint inhibitor, CTX-8371, and with other checkpoint inhibitors.

CTX-471 (CD137 or 4-1BB agonist antibody)

CTX-471, our monoclonal antibody product candidate, is a fully human, IgG4 monoclonal antibody that is an agonist of CD137, a key co-stimulatory receptor on immune cells.

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The CD137 antigenic site recognized by CTX-471 does not block the binding of CD137 ligand and is differentiated from the site recognized by CD137 antibodies from competitors.

We designed the antibody using different backbones and chose to use a human IgG4 backbone for CTX-471 to enable engagement of Fc receptors FcɣRI and FcɣRIIb to facilitate CD137 cross-linking while avoiding binding to FcɣRIIIa and depletion of immune effector cells through ADCC.

Immune cell depletion experiments showed that the activity of CTX-471 required the presence of CD4+ T-cells, CD8+ T-cells, and NK cells, indicating a coordinated involvement of both innate and adaptive immune cells.

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We also observed that tumors treated with CTX-471 had an approximate two-fold reduction in the number of immunosuppressive tumor-associated macrophages.

In addition, we have observed potent activity in other syngeneic tumor models including tumor eradication in the A20 model of lymphoma, the MC38 model of colon carcinoma and in the EMT6 model of breast cancer.

We believe that the ability of CTX-471 to transform the tumor microenvironment through the combined action of immune cell recruitment, alleviation of T-cell exhaustion, suppression of Tregs, and reduction of tumor suppressing macrophages leads to CTX-471’s antitumor activity in mouse models.

Phase 1 Clinical Trial of CTX-471

In a Phase 1b monotherapy study, CTX-471 was evaluated in patients with solid tumors that had progressed after at least three months on an approved PD-1 or PD-L1 inhibitor.

Initial results reported from the study included five clinical responses, including a durable PR in a patient with SCLC that converted to a complete response (as confirmed by PET scan) and four additional PRs (one unconfirmed) in patients with melanoma and mesothelioma.

The ORR in the subset of patients with advanced melanoma was 27% (3 of 11).

Data were presented at the American Society of Clinical Oncology (“ASCO”) Annual Meeting in June 2024.

Phase 1 Clinical Trial Data

In July 2019, we initiated a Phase 1 trial evaluating the safety and tolerability of CTX-471 as a monotherapy in patients with solid tumors who were previously treated with PD-1 or PD-L1 immune checkpoint inhibitors and subsequently relapsed or progressed after a period of stable disease.

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In the Phase 1a dose escalation, CTX-471 was observed to be generally well-tolerated in the Phase 1a stage of the trial.

The dose-limiting toxicity was two thrombocytopenia based on two observed events in Cohort 4, which was expanded from three to six patients to collect additional safety data.

The dose-limiting toxicity was thrombocytopenia.

Based on these results, 0.6 mg/kg was determined to be the maximum tolerated dose.

Phase 1b Dose Expansion

The dose expansion stage of the trial is completed.

In a Phase 1b monotherapy study, we evaluated CTX-471 in patients with solid tumors that had progressed after at least three months on an approved PD-1 or PD-L1 inhibitor.

60 patients with 17 different cancers were enrolled in the trial.

One patient (noted below) had a CR and four additional patients had a PR.

Of the four PRs observed in this dose expansion cohort, three PRs have been confirmed by RECIST 1.1 and the fourth PR was unconfirmed.

Initial results reported from the study included five clinical responses, including a durable PR in a patient with SCLC that converted to a complete response (as confirmed by PET scan) and four additional PRs (three confirmed by RECIST 1.1 and one unconfirmed) in patients with melanoma (3 out of 11 patients) and mesothelioma (1 out of 4 patients).

The ORR in the subset of patients with advanced melanoma was 27% (3 of 11).

There have been nine SAEs related to CTX-471 in the dose expansion stage of the trial.

All nine events resolved.

The responses observed as described below:

A PR was observed in a patient with metastatic melanoma who was previously treated with nivolumab and progressed on nivolumab.

Below is a series of CT scan images from this patient.

The patient had multiple metastases at baseline and reached a PR based on a 38% decline in linear tumor burden at week nine.

This PR was confirmed at week 17.

A PR was observed in a patient with metastatic melanoma of mucosal origin who was previously treated with first-line regimen of ipilimumab plus nivolumab followed by second-line nivolumab as a monotherapy.

After progressing on the prior regimens, the patient had joined the trial with multiple metastases at baseline.

This patient reached a PR based on a 58% decline in linear tumor burden at week 17.

This PR was not confirmed.

A PR was observed in a patient with mesothelioma.

This response was confirmed by RECIST 1.1.

A PR was observed in a patient with melanoma treated in the third line setting.

This response was confirmed by RECIST 1.1.

This patient has been on the study for more than 2 years and is still ongoing.

Data were presented at the American Society of Clinical Oncology (“ASCO”) Annual Meeting in June 2024.

The responses observed are described below:

Three PRs were observed in patients with metastatic melanoma among 11 patients with melanoma in the study.

Two of the PRs were confirmed and one was unconfirmed by RECIST 1.1.

A PR was observed in a patient with mesothelioma and confirmed by RECIST 1.1.

The CR was observed in a patient with advanced SCLC who was previously treated with the carboplatin/etoposide and atezolizumab (a PD-L1 blocker) regimen in the first line followed by a treatment with nivolumab (a PD-1 blocker) in the second line.

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Below is a series of CT scan images from this patient of the largest mass (RUL Lung) which was ~4 cm at baseline.

Of note, out of the five responses observed in this trial, three responses were in patients with melanoma, leading to a response rate of 27% in this subgroup of melanoma patients (3 out of 11).

The other responses were in mesothelioma (1 out of 4) and SCLC (1 out of 3).

Biomarker discovery

In November 2024, we presented novel biomarker data associated with CTX-471 at the 39th Society for Immunotherapy of Cancer (“SITC”) Annual Meeting.

Our research showed a correlation between the levels of neural cell adhesion molecule (“NCAM” or CD56) in baseline tumor cell biopsies and disease control in patients treated with CTX-471.

In November 2024, we presented novel biomarker data associated with CTX-471 at the 39th Society for Immunotherapy of Cancer (“SITC”) Annual Meeting demonstrating a correlation between the levels of neural cell adhesion molecule (“NCAM” or CD56) in baseline tumor cell biopsies and disease control in patients treated with CTX-471.

To measure pharmacodynamic effects, comparisons were made between pre- and post-CTX-471 treatment.

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These findings are novel in a clinical setting and support potential use of NCAM as a selection marker.

Development Plans for CTX-471

Based on the results of the monotherapy and combination arms of the Phase 1 trial, we are currently evaluating the design of a Phase 2 study of CTX-471 using NCAM as a biomarker, which we expect to initiate in mid-2025.

Additional Development Plans for CTX-471

Based on the results of the monotherapy and combination arms of the Phase 1 trial, we plan to initiate a Phase 2 study of CTX-471 using NCAM as a biomarker in mid-2026.

CTX-8371 (PD-1 x PDL-1 Bispecific Antibody)

CTX-8371 is a bispecific antibody that binds to both PD-1 and PD-L1, the targets of well-known and widely used checkpoint inhibitor antibodies.

Preclinical studies demonstrate that CTX-8371 has the ability to outperform PD-1, PD-L1, and combinations of the two to activate T-cells in in vitro assays.

Preclinical studies demonstrate that CTX-8371 has the ability to outperform PD-1 inhibitors, PD-L1 inhibitors, and combinations of the two to activate T-cells in in vitro assays.

In mouse xenografts, treatment with CTX-8371 led to significantly greater tumor growth control and longer survival than treatment with a PD-1 inhibitor alone, a PD-L1 inhibitor alone or the combination of PD-1 and PD-L1 inhibitors.

IND-enabling studies on CTX-8371, including GLP toxicology studies in non-human primates (“NHPs”) were completed in the first quarter of 2023.

The FDA cleared the IND for CTX-8371 in the fourth quarter of 2023 and the first patient in the Phase 1 clinical trial was dosed in April 2024.

CTX-8371 is a PD-1 x PD-L1 bispecific antibody

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While PD-1/PD-L1 checkpoint therapies have resulted in remarkable clinical efficacy across multiple cancer types, their efficacy, even in tumors with high immunogenicity, is limited to approximately 20% of patients.

Nevertheless, sales of checkpoint therapies in 2023 were estimated to be $48 billion.

Nevertheless, aggregate sales for checkpoint therapies is currently estimated to be approximately $50 billion.

There is no approved therapy that combines inhibition of both PD-1 and PD-L1 in the same molecule.

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The desire to improve the efficacy of PD-1/PD-L1 inhibitors has sparked multiple attempts to create bispecific antibodies in which one antigen binding site targets PD-1 or PD-L1 and the other targets immuno-oncology receptors such as CTLA-4, LAG-3 or CD137.

In contrast to those bispecific efforts described by others that have focused on a single pair of antigen-binding domains at a time, we have applied our StitchMabs TM technology to broadly screen for pairs of bispecific antigen-binding domains with the highest potential to generate antitumor activity.

Our efforts were enabled not only by the StitchMabs TM technology, but also by our investment in generating a broad portfolio of selective antibodies to approximately 40 potential immune targets across the innate and adaptive immune system.

In contrast to those bispecific efforts described by others that have focused on a single pair of antigen-binding domains at a time, we applied our StitchMabs TM technology in combination with our broad portfolio of selective antibodies to of immune targets across the innate and adaptive immune system to broadly screen for pairs of bispecific antigen-binding domains with the highest potential to generate antitumor activity.

We designed our combinatorial screen such that one antigen-binding domain was directed against PD-1, and the other selected from our library of candidate antibodies.

We screened these StitchMabs TM bispecific constructs in T-cell activation assays in the presence of PD-L1 expressing cells.

We screened these bispecific constructs in T-cell activation assays in the presence of PD-L1 expressing cells.

Our unbiased screening led us to an antibody that pairs a PD-1 binding domain and a PD-L1 binding domain.

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A simple model would suggest that inhibiting either PD-1 or PD-L1 should have approximately equal effects in this assay and there would be no advantage to inhibiting both.

Further investigation into the mechanism of CTX-8371 found that it led to T-cell activation through four mechanisms:

Further investigation into the mechanism of CTX-8371 found that it led to T-cell activation through four synergistic mechanisms:

Dual checkpoint blocker :

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Downregulation of PD-1 :

triggering the shedding of the extracellular domain of PD-1 receptors from the surface of T-cells resulting in a reduction in the levels of PD-1 on T-cells;

triggering the cleavage of the extracellular domain of PD-1 receptors from the surface of T-cells resulting in the conversion of PD-1 positive T-cells into PD-1 negative;

Indirect CD28 agonist:

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Differentiated mechanism of action of CTX-8371 drives enhanced T-cell activation

We also found that the greater activity of CTX-8371 in our T-cell activation assay compared to PD-1 inhibition also extended to PD-L1 inhibition.

Furthermore, CTX-8371 was associated with significantly more antitumor activity in a murine B16F10 melanoma model than was monotherapy with either a PD-1 inhibitor or a PD-L1 inhibitor or a combination of both.

Tumor growth in monotherapy-treated mice and in the combination PD-1 and PD-L1-treated mice was slowed to approximately half that observed with tumors in untreated mice.

In contrast, tumor growth was essentially stopped by the CTX-8371 bispecific antibody.

Treatment with CTX-8371 resulted in improved overall survival in this model and cured three of eight mice, such that their tumors were completely eradicated.

Tumor growth inhibition was improved when treating mice with CTX-8371 compared to treating them with monoclonal antibodies that inhibited either PD-1, PD-L1, or the combination of PD-1 and PD-L1

Dosing with CTX-8371 led to improved overall survival in a B16F10 melanoma model compared to either PD-1 or PD-L1 checkpoint inhibitors or to the combination of both

CTX-8371 also reduced tumor growth in the syngeneic MB49 bladder cancer model and in the syngeneic EMT-6 breast cancer models which are known to be non-responsive to checkpoint blocker treatments.

Dosing with CTX-8371 led to tumor growth inhibition in the syngeneic EMT-6 breast cancer model and in the syngeneic MB49 bladder cancer model

In April 2022, we presented preclinical data on CTX-8371’s potential unique mechanism of action ("MOA") that involves cleavage of cell surface PD-1, at the 2023 American Association for Cancer Research ("AACR") annual meeting.

A summary of the results are as follows:

Treatment with CTX-8371 led to PD-1 loss from the surface of intra-tumoral T cells in tumor-bearing transgenic hPD-1/h-PD-L1 mice, and on peripheral blood T cells in cynomolgus monkeys;

this unique MOA differentiates CTX-8371 from marketed inhibitors targeting either PD-1 or PD-L1

Clearance and half-life of CTX-8371 were within the expected ranges for a human IgG1 antibody in NHPs with a linear PK

Treatment with CTX-8371 in the aggressive MC38-hPD-L1 colorectal mouse model led to a dose-proportional reduction in tumor volume and a complete eradication of tumors at the highest dose

Taken together, the murine and cynomolgus monkey PK data, receptor occupancy data, and in vivo efficacy data in murine models was used to calculate the predicted human efficacious dose range for CTX-8371

Phase 1 and Development Plans for CTX-8371

We submitted an IND to the FDA in the third quarter of 2023.

This IND was cleared by the FDA in October 2023.

In the first quarter of 2024 we initiated a first-in-human Phase 1 study of CTX-8371 in patients with metastatic or locally advanced malignancies.

This Phase 1 trial is a multiple ascending, dose escalation and there are five doses planned in this study:

This Phase 1 trial is a multiple ascending, dose escalation with five doses:

0.1, 0.3, 1.0, 3.0 and 10 mg/kg.

Patients eligible to participate in the trial are patients who progressed while receiving an approved PD-1 or PD-L1 inhibitor.

Other eligibility criteria include patients with metastatic of locally advanced melanoma, non-small cell lung cancer, head and neck cancer, Hodgkin’s Lymphoma and triple negative breast cancer.

As of January 2025, the third cohort of this trial was fully enrolled with no dose limiting toxicities observed.

Initial data from the trial is expected in the second half of 2025.

The study includes patients who progressed while receiving an approved PD-1 or PD-L1 inhibitor.

Other eligibility criteria include patients with metastatic or locally advanced melanoma, non-small cell lung cancer (“NSCLC”), head and neck cancer (“HNCC”), Hodgkin’s Lymphoma (“HL”) and triple negative breast cancer (“TNBC”).

In the Phase 1 dose-escalation study, CTX-8371 demonstrated 3 confirmed responses out of 15 patients, including patients with both solid tumor and hematologic malignancies:

NSCLC, TNBC and HL.

The patient with NSCLC achieved complete resolution of all measurable target tumor lesions, and the patient with TNBC achieved over 90% reduction in target tumor lesions.

No dose limiting toxicities were observed at any dose level.

CT scans from the responding patient with NSCLC are below:

CT scans from the responding patient with TNBC are below:

Cohort expansions for CTX-8371 are now enrolling patients with TNBC (n=28) and NSCLC (n=28) with an expansion cohort in patients with HL (n=12) expected to begin shortly, all in the post-checkpoint inhibitor setting.

Half of the patients with each tumor type will be dosed at 3.0 mg/kg and half will be dosed at 10.0 mg/kg.

Initial data from these cohort expansions, as well as available data from the Phase 1 dose-escalation portion of the study, are expected to be presented at a major medical conference in the first half of 2026.

CTX-10726 (PD-1 x VEGF-A Bispecific Antibody)

CTX-10726 is a novel, tetravalent PD-1 x VEGF-A bispecific antibody that we discovered, engineered and developed since 2023.

CTX-10726 is a novel, tetravalent PD-1 x VEGF-A bispecific antibody that we discovered, engineered and developed at Compass.

CTX-10726 is designed to synergistically deliver VEGF-A blockade and checkpoint inhibition, which is potentially applicable to multiple solid tumor indications.

CTX-10726 utilizes a fully human, glycosylated IgG1 with silenced Fc-γ receptor binding and demonstrates a highly stable structure with high affinity target binding.

CTX-10726 utilizes a fully human IgG1 with silenced Fc-γ receptor binding and demonstrates a highly stable structure with high affinity target binding.

Based on preclinical studies, CTX-10726 exhibits several-fold more potent PD-1 blockade compared with publicly available data reported for other drugs in the class, and we believe this may be a key differentiator from comparable bispecifics.

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tovecimig, which contains a VEGF-A targeted component, and CTX-8371, which contains a PD-1 targeted component.

We are continuing IND-enabling studies and expect to file an IND by the end of 2025.

CTX-10726 is a PD-1 x VEGF-A bispecific antibody

Early-Stage Discovery

Traditionally, our approach to early-stage discovery has been based on the observation that traditional methods of antibody discovery are slow, inefficient, and are limited by lack of diversity of antigenic sites, or epitopes, that are recognized using these methods.

We believe these limitations impair drug developers’ ability to identify the best product candidates.

We have created several technological solutions that are designed to address the key challenges in antibody development with the goal of incorporating our solutions into bispecific product candidates.

First, we developed and acquired several complementary platforms that enable us to generate antibodies with a high level of epitope diversity and excellent physical and biochemical properties.

Second, we have developed sophisticated technologies to screen our antibody sets in functional biological assays designed to prioritize antibodies with desirable biological activities.

Third, we have developed our proprietary StitchMabs TM technology that allows us to rapidly evaluate the potential of the antibodies we discover in a bispecific antibody format.

We have also developed a proprietary transgenic mouse line that produces antibodies with the differentiated property that they all share a human common light chain.

We imposed this restriction at the earliest stage of our bispecific antibody discovery process in anticipation of the need to simplify the manufacturing of our bispecific product candidates.

Sharing a common light chain enables our bispecific antibodies to be manufactured using a well-established process that has been successfully used by the biopharmaceutical industry to produce monoclonal antibodies at commercial scale, thereby avoiding the complexities associated with the manufacture of bispecific products that lack this property.

We found that imposing this restriction on the construction of the antibody pool did not hinder our ability to obtain highly potent and selective antibodies.

We have focused exclusively on modulation of the immune system through the development of novel antibody therapeutics.

Antibodies are structurally distinct Y-shaped proteins formed through the pairing of two long proteins, called heavy chains, and two short proteins, called light chains.

Each heavy and light chain pair forms a binding site where the antibody specifically binds its target, which is also known as an antigen.

The immune system is capable of not only fighting foreign invaders, but also of recognizing and eliminating a human body’s own cells that have become pathogenic after transformation, such as in cancer.

There are two broad classes of antibodies used in cancer therapy.

The majority of antibodies directly target the tumor or its surroundings.

The more recent class consists of antibodies that modulate the immune system leading to immune-mediated killing of tumors.

These antibody drugs mainly exert this effect via a single modulation of the immune system.

We believe that modulation of more than one function of the immune system simultaneously has the potential to improve the therapeutic benefit and utility of immuno-oncology therapies.

Antibodies can be generated in many ways, and multiple companies claim to possess proprietary antibody discovery platforms, each with specific advantages.

Our antibody platform was designed with a broad set of capabilities and resources that we can leverage with the goal of generating a portfolio of highly distinct bispecific products.

Our approach to bispecific antibody discovery encompasses four principles:

antibody diversity is required to generate a representative sample of possible therapies;

functional screening is critical to identifying optimal solutions;

a combinatorial approach enables parallel assessment of many potential bispecific antibodies;

decisions made at the start of the discovery process have a major impact on successful clinical and commercial-scale manufacturing.

Antibody diversity

We obtained our initial pools of antibodies from multiple internally-developed platforms, including our custom phage display library and our transgenic mouse line.

We constructed our phage display library based on the peripheral B cell diversity of 70 healthy human donors.

This system allows us to generate large and highly diverse sets of antibodies that are fully human;

target multiple epitopes on a target of interest;

and possess excellent physical and biochemical properties.

We describe these antibodies as having good ‘drug-like’ properties.

To generate additional antibody candidates, we can also immunize a proprietary line of humanized transgenic mice with antigens of interest to isolate a diverse set of fully human antibodies that share a common human light chain, but distinct native mouse heavy chains.

We estimate that the pool of antibodies from these two platforms represents over 10 10 unique sequences.

We have expressed libraries of antibodies against any particular target using our Human Display technology which streamlines the expression of functional antibodies such that each cell expresses only one antibody clone.

We then further screen our diverse sets of antibodies expressed with our Human Display technology to fine-tune for specificity.

Sequence changes can be readily introduced to further optimize leads from our screens.

Our ability to generate viable antibody candidates, with good drug-like properties and high manufacturability potential in a high-throughput manner has enabled us to rapidly assemble a portfolio of proprietary antibodies to over 40 key innate and adaptive immune targets and tumor antigens.

This portfolio of antibodies is designed to provide us with a set of well-characterized antibodies that can be incorporated into our combinatorial bispecific antibody screening platform.

We have discovered proprietary antibodies that modulate two key components of the immune system:

innate immunity and adaptive immunity as well as antibodies to selected antigens on tumor cells.

This expansive collection of antibodies allows us to use our proprietary technologies to uncover unexpected synergies.

Functional Screening

A critical part of our antibody discovery process is our ability to produce sufficient quantities of purified antibodies to assess their biological activities both in cells and, in some cases, animal models.

Our human display technology allows us to efficiently express full-length antibodies on cell surface, thereby facilitating the high throughput screening of our antibodies across multiple functional screens.

While we do assess standard biochemical parameters such as binding affinity and specificity as part of the initial screening of our candidate sets, we note that activity in a complex biological system cannot be predicted based on physical and biochemical parameters alone.

We have shown with CTX-471, for example, that activity in a complex biological system cannot necessarily be predicted on strictly biochemical parameters.

StitchMabs TM Technology

A natural antibody recognizes a single target antigen and is therefore monospecific.

Because a natural antibody features two identical binding sites, it is considered bivalent for that target.

Although natural antibodies recognize a single target antigen, it is possible to engineer antibodies so that their two binding sites bind two different targets.

The construction of a bispecific antibody typically requires a significant investment in cloning, construct optimization, protein expression, and protein purification before the therapeutic potential of any particular bispecific antibody can be assessed.

In practice, these requirements mean that the diversity of antigen pairs targeted by bispecific antibodies is limited, and development is oftentimes prioritized for antigen pairs suggested by existing scientific literature.

Our proprietary StitchMabs TM technology is a novel screening approach which we developed to assess the potential of any pair of antigen-binding sites in a bispecific antibody format.

This combinatorial antibody-linking technology stably and irreversibly attaches a second pair of antigen-binding domains to a standard antibody during a 15-minute incubation at room temperature.

The resulting stitched antibody acts structurally and functionally like a bispecific antibody.

StitchMabs TM allows us to assess our large library of antigen-binding domains in combinatorial fashion.

Once we have generated and purified large numbers of bispecific candidates, we then assess the potential of these candidates in functional assays and determine whether these bispecifics have additive, reductive or synergistic activity.

Screening of these bispecific molecules in functional assays has led us to discover novel product candidates with unexpected synergistic activity in cellular and animal models.

Common Light Chain Platform

The embedded common light chain feature in our antibodies greatly simplifies the manufacture of our bispecific product candidates.

Most antigen-binding domains of antibodies are composed of a heavy chain and a light chain that have been optimized together to recognize a specific antigen.

If these two chains are expressed independently, as is the case with most antibody manufacturing processes, they are often reassembled in various ways, leading to heterogenous mixture of the desired product along with peptide segments corresponding to two heavy chains and two light chains.

Separation of the desired product from the mixture is a technically challenging and expensive process.

We address this challenge by including only common light chain compatible antibodies as part of our antibody discovery process for potential incorporation into bispecifics.

The variability in the antigen-binding domain of our antibodies in the heavy chain is sufficient to generate a diverse, potent, selective, and functionally active set of antibodies.

We further simplified the manufacturing of our bispecific antibodies by assembling a single heavy chain construct that encodes both antigen-binding domains.

As a result, the manufacturing of our bispecifics closely resembles that of standard monoclonal antibodies, which include one heavy chain and one light chain.

Our focus on common light chain antibodies simplifies the process of converting our StitchMabs TM screening candidates into bispecific antibody product candidates.

A common light chain simplifies the production of bispecific antibodies

In the first quarter 2026, we received FDA clearance for the IND for CTX-10726 and the Phase 1 study will be open for enrollment in Q1 2026.

This Phase 1 multiple ascending dose-escalation study of CTX-10726 will include four doses (0.3, 1.0, 3.0, and 10.0 mg/kg) in a 3+3 format.

The multi-center study will enroll patients with locally advanced, unresectable or metastatic malignancies, including renal cell carcinoma, gastroesophageal cancer, hepatocellular carcinoma, and endometrial cancer, in whom standard of care therapies have failed.

Discovery and Preclinical Activity for CTX-10726

CTX-10726 showed high-affinity binding to both human and cynomolgus monkey VEGF-A and PD-1.

CTX-10726 effectively blocked VEGF-A/VEGFR2 and PD-1/PD-L1 interactions in a dose dependent manner and showed reduced engagement with Fcγ receptors, limiting off-target immune activation.

Functionally, it significantly enhanced IFN-γ production in MLRs and tumor cell killing by activated PBMCs.

In vivo, CTX-10726 outperformed benchmark biosimilar anti-VEGF or PD-1 antibodies in controlling tumor growth across multiple xenograft and syngeneic models.

The dual blockade of PD-1 and VEGF-A by CTX-10726 produced superior anti-tumor activity compared to anti-VEGF-A treatment or ivonescimab (****, P <0.0001, Two-way ANOVA), demonstrating enhanced in vivo potency in the following model:

Human NSCLC (HCC827) Xenografts

Treated with human PBMCs and indicated antibodies

Testing both PD-1 and VEGF-A targeting

License Agreements

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Our wholly owned subsidiary Trigr Therapeutics, Inc.

(“TRIGR”) and ABL Bio, a South Korean biotechnology company, entered into an exclusive global (excluding South Korea) license agreement (the “TRIGR License Agreement”) which granted TRIGR a license to ABL001, ABL Bio’s bispecific antibody targeting DLL4 and VEGF-A (renamed CTX-009 and subsequently tovecimig).

Under the terms of the agreement, ABL Bio and TRIGR would jointly develop tovecimig, with ABL Bio responsible for development of tovecimig throughout the end of Phase 1 clinical trials and TRIGR responsible for the development of tovecimig from Phase 2 and onward.

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CTX-471 (CD137 agonist antibody)

We entered into an amended and restated collaboration agreement with Adimab, LLC ("Adimab"), dated February 11, 2015, as amended.

This agreement relates to our license from Adimab for certain antibodies for development and commercialization as biopharmaceutical products, including our product candidate, CTX-471.

We entered into an amended and restated collaboration agreement with Adimab, LLC ("Adimab"), dated February 11, 2015.

This agreement relates to our license from Adimab for certain antibodies for development and commercialization as biopharmaceutical products, including our acquired product candidate, CTX-471.

We were granted an exclusive option to license and potentially acquire antibodies under the agreement, which we exercised with respect to CTX-471.

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patent that covers an FDA approved drug may also be eligible for patent term extension, which permits patent term restoration as compensation for the patent term lost during the FDA regulatory review process.

The Hatch Waxman Act permits a patent term extension of up to five years beyond the expiration of the patent.

The Hatch-Waxman Act permits a patent term extension of up to five years beyond the original expiration of the patent.

The length of the patent term extension is related to the length of time the drug is under regulatory review.

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Our patent estate includes patent applications with claims relating to our product candidates, methods of use and manufacturing processes, and claims for potential future products and developments.

As of January 31, 2025, we have greater than 90 issued patents and patent applications pending in the United States and foreign jurisdictions relating to tovecimig, CTX-471, CTX-8371, CTX-10726 and other discovery and research programs.

We have 7 patents issued in the United States and issued patents in Taiwan, China, Eurasia, Japan, Korea, Malaysia, Singapore and New Zealand related to our CTX-471 program, and 2 patents issued in the United States, and issued patents in China, Japan and Taiwan, related to our CTX-8371 program.

As of January 31, 2026, we have nearly 100 issued patents and patent applications pending in the United States and foreign jurisdictions relating to tovecimig, CTX-471, CTX-8371, CTX-10726, and other discovery and research programs.

We have 7 patents issued in the United States and 23 issued patents in Taiwan, China, Eurasia, Japan, Korea, Malaysia, Singapore and New Zealand related to our CTX-471 program, and 3 patents issued in the United States, and 8 issued patents in China, Japan, Malaysia, Mexico, and Taiwan, related to our CTX-8371 program.

We also have access to patents issued in Australia, Europe and the United States related to our antibody and display programs, as well as 27 patents issued in Australia, Canada, China, Europe, Japan, Korea, Russia and 2 in United States related to our tovecimig program.

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We own 4 pending patent families with 10 issued U.S.

patents and issued patents in Taiwan, China, Eurasia, Japan, Korea, Malaysia, Singapore, and New Zealand, 3 U.S.

patents and issued patents in Taiwan, China, Eurasia, Israel, Japan, Korea, Malaysia, Mexico, Singapore, and New Zealand, 3 U.S.

patent applications, and 35 patent applications in foreign jurisdictions, related to our CD137 agonist antibody therapeutic platform including, but not limited to, our CTX-471 therapeutic candidate.

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We own 1 pending patent family with 3 issued U.S.

patents, issued patents in China, Japan, and Taiwan, 1 U.S.

patents, issued patents in China, Japan, Malaysia, Mexico, and Taiwan, 1 U.S.

patent application, and 21 patent applications in foreign jurisdictions, related to our PD-1/PD-L1 bispecific antibody therapeutic platform including, but not limited to, our CTX-8371 therapeutic candidate.

Patents that grant from these patent families are generally expected to start to expire in 2039, subject to possible patent term extension.

We own, or have an ownership interest in, 2 pending patent families with 2 U.S.

pending patent applications and 3 patent applications in foreign jurisdictions, related to our CD277 discovery and research programs.

We own, or have an ownership interest in, 2 pending patent families with 1 issued patent in the U.S., 1 U.S.

pending patent application and 2 patent applications in foreign jurisdictions, related to our CD277 discovery and research programs.

Patents that grant from these patent families are generally expected to start to expire in 2039, subject to possible patent term extension.

We own 1 pending patent family with 1 U.S.

pending patent application and 1 patent application in foreign jurisdictions related to our antibody and display programs including, but not limited to, common light chains.

We own 1 pending patent family with 1 issued U.S.

patent and 1 patent application in foreign jurisdictions related to our antibody and display programs including, but not limited to, common light chains.

Patents that grant from this patent family are generally expected to start to expire in 2039, subject to possible patent term extension.

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In addition to these marketed therapies, numerous compounds are in clinical development for the potential treatment of cancer.

Biliary tract cancers are aggressive and rare gastrointestinal cancers that have a very poor prognosis.

First line treatment of locally advanced or metastatic BTC includes the chemotherapy combination of gemcitabine and cisplatin, often with the addition of the PD-1 inhibitor Imfinzi® (durvalumab).

Biliary tract cancers are aggressive gastrointestinal cancers that have a very poor prognosis.

First line treatment of locally advanced or metastatic BTC includes the chemotherapy combination of gemcitabine and cisplatin, often with the addition of the PD-L1 inhibitor Imfinzi® (durvalumab) or PD-1 inhibitor Keytruda (pemrolizumab).

In September of 2022, AstraZeneca received FDA approval of durvalumab in combination with gemcitabine/cisplatin for the first line treatment of BTC.

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The only FDA approved therapies for second line treatment of BTC are targeted therapies that address specific tumor mutations or solid tumors that are microsatellite instability high.

For example, in November 2024, Jazz Pharmaceuticals received FDA approval of ziihera for previously treated, unresectable, or metastatic human epidermal growth factor receptor (“Her-2”) positive biliary tract cancer, which may be beneficial to the small subset of patients in whom Her-2 is amplified.

We believe that the combination of all targeted therapies are appropriately 10-15% of BTC patients.

For example, in November 2024, Jazz Pharmaceuticals received FDA approval of Ziihera (zanidatamab-hrii) for previously treated, unresectable, or metastatic human epidermal growth factor receptor (“HER2”) positive (IHC 3+) biliary tract cancer, which may be beneficial to the small subset of patients in whom HER2 is amplified overexpressed.

We believe that the combination of all targeted therapies are appropriately 10-15% of patients with BTC.

Colorectal cancer is the second most common cause of cancer deaths in the United States and constitutes approximately 10% of all annually diagnosed cancer and cancer related deaths globally.

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Subject to receiving marketing approval, we intend to maximize the value of our product candidates by either independently planning to pursue the commercialization of our products in one or more major geographies by building an internal sales and marketing organization, or by seeking collaborations with third parties with commercialization infrastructure.

At the appropriate time in the future, and if one or more of our product candidates continues to advance successfully in development and enter registrational trials, we also plan to build a marketing and sales management organization to create and implement marketing strategies for any product candidates that we would potentially market through our own sales organization and to oversee and support our sales force.

The responsibilities of such marketing organization would include developing educational initiatives with respect to approved products and establishing relationships with researchers and practitioners in relevant fields of medicine.

Manufacturing

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Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

Sponsors of applicable clinical trials of FDA-regulated products are required to register and disclose certain clinical trial information within specific timeframes for publication on www.clinicaltrials.gov.

Sponsors also must disclose certain results of these clinical trials, although disclosure of results may be delayed until after the new product or new indication has been approved by the FDA.

Competitors may use this publicly available information to gain knowledge regarding the progress of development programs, as well as clinical trial design.

Failure to timely register a covered clinical study or to submit study results as provided for in the law can give rise to public notifications of noncompliance, civil monetary penalties, and also prevent the non-compliant party from receiving future grant funds from the federal government.

Submission of a BLA to the FDA

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

Additionally, for molecularly targeted cancer drugs, beginning after February 3, 2029, the FDA may require testing of certain novel single ingredient or combination regimens to yield clinically meaningful pediatric study data that is gathered using appropriate formulations for each age group for which the study is required, including dosing, safety, and preliminary efficacy to inform potential pediatric labeling.

Pediatric exclusivity is another type of non-patent exclusivity in the United States and, if granted for a biologic, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity for all formulations, dosage forms, and indications of the biologic, including the five-year and three-year non-patent and orphan exclusivity.

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rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted.

If reports of FDA-requested pediatric trials are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent protection covering the product are extended by six months.

This is not a patent term extension, but it effectively extends the regulatory period during which the FDA cannot accept or approve another application relying on the BLA sponsor’s data.

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Biosimilars and Exclusivity

The Patient Protection and Affordable Care Act ("Affordable Care Act"), signed into law on March 23, 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009 ("BPCI"), which created an abbreviated approval pathway for biological products shown to be similar to, or interchangeable with, an FDA-licensed reference biological product.

This amendment to the PHSA attempts to minimize duplicative testing.

The Patient Protection and Affordable Care Act ("Affordable Care Act"), signed into law on March 23, 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009 ("BPCIA"), which created an abbreviated approval pathway for biological products shown to be similar to, or interchangeable with, an FDA-licensed reference biological product.

This amendment to the Public Health Service Act (“PHSA”) attempts to minimize duplicative testing.

Biosimilarity, which requires that there be no clinically meaningful differences between the proposed biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical trial or trials.

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Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition.

If a product receives multiple orphan designations or has multiple approved indications, it may not qualify for the orphan drug exemption.

Under the One Big Beautiful Bill Act of 2025, this restriction was eliminated;

and effective for the 2028 initial price applicability year, all orphan drugs, regardless of the number of orphan drug designations or indications, are exempt from the Medicare drug price negotiation program.

The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.

The effect of IRA on our business and the healthcare industry in general is not yet known.

On April 15, 2025, the Trump administration published Executive Order 14273, “Lowering Drug Prices by Once Again Putting Americans First,” which generally directs the federal government to take measures to reduce drug prices, including eliminating the so-called “pill penalty” under the IRA that creates a distinction between small molecule and large molecule products for purposes of determining when a drug may be eligible for drug price negotiation.

On May 12, 2025, the Trump administration published Executive Order 14297, “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients” which generally, among other things, directs the federal government to establish and communicate most-favored-nation (“MFN”) price targets to pharmaceutical manufacturers to bring prices for American patients in line with comparably developed nations.

Further, the Executive Order directs the federal government to support regulatory paths to allow direct-to-patient sales for companies that meet these targets.

It also states that the Administration will take additional aggressive action (for example, examining whether marketing approvals should be modified or rescinded or opening the door for individual drug importation waivers) should manufacturers fail to offer American consumers the MFN lowest price.

It also directs the Secretary of Commerce and the U.S.

Trade Representative to “take all necessary and appropriate action to ensure foreign countries are not engaged in any act, policy, or practice that may be unreasonable or discriminatory or that may impair United States national security .

including by suppressing the price of pharmaceutical products below fair market value in foreign countries.” Notably, a similar “Most Favored Nation” pricing rule enacted under the first Trump administration was subject to an injunction resulting from judicial challenges to the rule, which was formally rescinded by the former Biden Administration in August 2021.

On December 19, 2025, CMS released two proposed rules that would incorporate MFN pricing principles into federal reimbursement for prescription drugs.

The first proposal, the Global Benchmark for Efficient Drug Pricing Model (“GLOBE”) for Medicare Part B, would require manufacturers of specified single source drugs and sole source biologics to pay incremental rebates based on international benchmark prices, with participation triggered for products meeting CMS’s spending and eligibility criteria.

The second proposal, the Guarding U.S.

Medicare Against Rising Drug Costs (“GUARD”) model for Medicare Part D, would similarly mandate manufacturer rebates for qualifying sole source drugs where the Medicare net price exceeds an MFN benchmark derived from international reference pricing methodologies.

As proposed, GLOBE would begin a five year performance period on October 1, 2026 and GUARD would begin its performance period in 2027.

These proposals will likely be subject to legal challenges that could delay their implementation or modify their impact on manufacturer pricing and revenue.

Additionally, in November 2025, CMS introduced the GENErating cost Reductions fOr U.S.

Medicaid (“GENEROUS”) Model, a voluntary MFN framework for manufacturers participating in the Medicaid Drug Rebate Program.

Although it is voluntary, the GENEROUS Model could also impact the drug pricing landscape for manufacturers.

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

Certain states are also pursuing cost containment efforts through Prescription Drug Affordability Boards (“PDABs”) and similar entities.

While many PDABs have been granted authority to promote drug price transparency and reporting, some states have granted PDABs more expansive authority, including to set Upper Payment Limits (“UPLs”) on select, high price drugs.

The adoption and implementation of UPLs may put downward pressure on drug prices and impact our company’s future revenues.

Other Healthcare Laws and Compliance Requirements

46 unchanged sentences

The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase shareholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

As an emerging company operating in a competitive industry, much of our success is rooted in the diversity of our teams and our commitment to inclusion.

As a company operating in a competitive industry, much of our success is rooted in the diversity of our teams and our commitment to inclusion.

We value diversity at all levels and continue to focus on extending our diversity and inclusion initiatives across our entire workforce, from working with managers to develop strategies for building diverse teams to promoting the advancement of leaders from different backgrounds.

14 unchanged sentences

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