Cybrexa Therapeutics Announces First Patient Dosed with First-in-Class Peptide-Drug Conjugate CBX-12 in Phase 2 Trial in Ovarian Cancer

Primary target patient population for the CBX-12 Phase 2 study is women with platinum-resistant or refractory ovarian cancer who are naïve to TOP1-targeted agents

Study initiation follows positive Phase 1 study results, which showed a 40% response rate in TOP1-naïve ovarian cancer patients, in addition to activity across five other solid tumor types and a favorable safety profile

Trial marks key milestone in driving pipeline progress with multiple Phase 2 programs planned for CBX-12 in 2025 as a monotherapy and in combination

NEW HAVEN, Conn. – October 7, 2024 – Cybrexa Therapeutics, a clinical-stage oncology biotechnology company developing a novel class of tumor-targeting peptide-drug conjugate (PDC) therapeutics, today announced that the first patient has been dosed in a Phase 2 clinical trial evaluating CBX-12 in patients with platinum-resistant or refractory ovarian cancer. CBX-12 is a first-in-class PDC that uses Cybrexa’s proprietary alphalex™ technology to enhance the delivery of exatecan, a potent, established topoisomerase 1 (TOP1) inhibitor, directly to tumor cells while sparing healthy tissue. This trial initiation follows promising Phase 1 results, which demonstrated CBX-12’s broad activity across ovarian, breast, non-small cell lung cancer (NSCLC), thymic, gallbladder, and colorectal cancers along with a manageable safety profile.

“Dosing the first patient marks an important milestone for the Phase 2 clinical trial in ovarian cancer and for patients facing this aggressive disease,” said Per Hellsund, President and Chief Executive Officer of Cybrexa. “CBX-12 recently demonstrated significant antitumor activity, broad application potential, and a favorable safety profile in a Phase 1 study, including encouraging response rates in TOP1-naïve ovarian and breast cancer patients. We are particularly excited about the potential for CBX-12 not only as a standalone treatment but also as a promising candidate for future combination therapies and look forward to its continued advancement in this and additional Phase 2 studies in solid tumors, which are planned for 2025.”

The Phase 2 trial is a randomized, open-label study designed to evaluate the safety, tolerability, and efficacy of CBX-12 in women with platinum-resistant or refractory ovarian cancer at two doses: 125 mg/m² every 21 days or 100 mg/m² every 21 days.

Cybrexa plans an additional Phase 2 study of CBX-12 in colorectal cancer in 2025 in collaboration with the National Cancer Institute (NCI), as well as other Phase 2 studies evaluating CBX-12 as a monotherapy and in combination across a range of solid tumors. Leveraging its alphalex platform to develop multiple promising assets in oncology, Cybrexa is progressing its broader pipeline, including CBX-15, which is expected to enter the clinic in 2025 for the treatment of solid tumors using MMAE (monomethyl auristatin E) as its payload.

Unlike antibody-drug conjugates, CBX-12 does not rely on antigen expression for targeting but rather uses a pH-low insertion peptide (pHLIP ^®) to selectively deliver its payload into the cytoplasm of cancer cells. Results from the Phase 1 study demonstrated that CBX-12 is well tolerated and exhibits promising activity across a range of advanced or metastatic solid tumors, highlighting the versatility of the alphalex platform and its ability to enhance the delivery of cancer therapeutics while limiting off-target effects. The Phase 1 study results were recently presented at the European Society for Medical Oncology Congress (ESMO 2024) in a poster session.

To learn more about the Phase 2 study of CBX-12, please visit ClinicalTrials.gov (NCT06315491).

About CBX-12

CBX-12 is a first-in-class peptide-drug conjugate (PDC) that utilizes Cybrexa’s proprietary alphalex™ technology to enhance delivery of exatecan to tumor cells and is composed of a pH-Low Insertion Peptide (pHLIP^®), a linker, and exatecan. CBX-12 is designed to increase the efficacy and reduce the toxicity of topoisomerase 1 inhibition by delivering exatecan, a highly potent, second-generation topoisomerase 1 inhibitor, directly to the tumor cells. As an antigen-independent therapy, CBX-12 may have broad utility in patients who are not eligible for antigen-targeted therapies, including monoclonal antibodies and antibody-drug conjugates (ADCs), and has potential for use in combination regimens with other anti-cancer agents and immunotherapies.

About the alphalex™ Technology Platform

The Cybrexa alphalex technology is a novel antigen-independent, peptide-drug conjugate platform that enables targeted delivery of highly potent anti-cancer treatments and aims to revolutionize the standard of care in oncology. The platform consists of a pH-Low Insertion Peptide (pHLIP^®), a linker, and a small molecule anti-cancer agent. pHLIP peptides are a family of pH-low insertion peptides that target acidic cell surfaces. pHLIP was developed at Yale University and the University of Rhode Island and is exclusively licensed to pHLIP, Inc., and Cybrexa is a sublicensee of pHLIP, Inc.

About Cybrexa Therapeutics

Cybrexa is a privately held clinical-stage biotechnology company pioneering novel antigen-independent, tumor-targeting peptide-drug conjugate (PDC) therapeutics. The company is led by a dynamic team of highly successful life science entrepreneurs and veteran drug development scientists. Cybrexa is on a mission to create therapeutics that revolutionize the standard of care in oncology, and its robust pipeline aims to combat breast, ovarian, non-small cell lung cancer, and a range of other tumors. Its assets are built on Cybrexa’s alphalex™ technology platform, which enables intracellular delivery of highly potent anti-cancer treatments. Cybrexa is based in New Haven, Connecticut and was founded in 2017. For more information, please visit www.cybrexa.com or follow us on LinkedIn and X.

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Investor Contact:
Per Hellsund, CEO, Cybrexa Therapeutics
860-717-2731
[email protected]

Media Contact:
Robin Fastenau, Scient PR
[email protected]

Cybrexa Therapeutics Announces Positive Final Data at ESMO 2024 from Phase 1 Study of Peptide Drug Conjugate CBX-12 in Advanced Solid Tumors

• Data demonstrate broad activity of CBX-12 across six tumor types with a strong response rate in TOP1-naïve patients with ovarian (40%; N=10) and HR+ HER2- breast (43%; N=7) cancer, in addition to a favorable safety profile
• Phase 2 study in platinum-resistant ovarian cancer initiated in Q3 2024

NEW HAVEN, Conn. – September 16, 2024 – Cybrexa Therapeutics, a clinical-stage oncology biotechnology company developing a novel class of tumor-targeting peptide drug conjugate (PDC) therapeutics, today announced positive final results from its Phase 1 clinical trial of CBX-12 (alphalex™ exatecan). These data demonstrate that CBX-12 is well tolerated and exhibits promising activity across a range of advanced or metastatic solid tumors, including ovarian, breast, thymic, gall bladder, non-small cell lung cancer (NSCLC) and colorectal cancers, underscoring its potential as a highly differentiated conjugate with broad antitumor activity. The study results were presented in a poster session at the European Society for Medical Oncology (ESMO) Congress 2024.

“These Phase 1 study results highlight the potential of our alphalex™ Platform to create meaningful therapies that deliver a payload with an improved therapeutic index while sharply reducing the toxicities that often limit conventional therapies,” said Per Hellsund, President and Chief Executive Officer of Cybrexa. “We believe CBX-12 marks a new era in cancer therapy that potentially offers precision targeting and enhanced drug delivery that could redefine patient outcomes. These data support the continued development of CBX-12 across a wide range of tumor types, validating the broad applicability of the platform, and led us to initiate a randomized Phase 2 study in platinum-resistant ovarian cancer patients. Additional Phase 2 studies in solid tumors are planned to begin in 2025.”

CBX-12 is designed to deliver higher concentrations of exatecan, a topoisomerase 1 (TOP1) inhibitor, directly to tumor cells while sparing healthy tissue. Unlike antibody-drug conjugates, CBX-12 doesn’t rely on antigen expression for targeting but rather uses a pH-low insertion peptide (pHLIP) to selectively deliver its payload into the cytoplasm of cancer cells.

“In this study of CBX-12, we’ve seen encouraging clinical activity across six tumor types, including exciting response rates in TOP1-naïve ovarian and breast cancer patients,” said Mike  Needle, M.D., Chief Medical Officer of Cybrexa. “Importantly, the manageable safety profile of CBX-12 further enhances its potential not only as a standalone treatment but also as a promising candidate for future combination therapies. By bypassing the need for antigens and focusing on a universal feature of tumor microenvironments, we believe CBX-12 could benefit a larger population than currently available therapies.”

Study Highlights

The Phase 1 study of CBX-12 demonstrated significant antitumor activity, broad application potential, and a favorable safety profile in patients with various advanced and metastatic cancers.

Efficacy:

• CBX-12 treatment resulted in activity across multiple different types of solid tumors, including breast, ovarian, NSCLC, colorectal (CRC), thymic and gallbladder cancers.
• Responses were observed in ovarian cancer, breast cancer, NSCLC and CRC.
• Specifically, in 10 ovarian cancer patients who were TOP1-naïve, there was one confirmed complete response, one confirmed partial response (PR), and two unconfirmed PRs, with eight out of 12 patients showing clinical benefit.
• In seven TOP1-naïve breast cancer patients, there were two confirmed PRs and one unconfirmed PR. All evaluable breast participants were HER-2 negative and HR positive.

Safety:

• The most frequent treatment-related adverse events included anemia (53.6%, with 24.6% Grade 3-4), leukopenia (42.0%, with 21.7% Grade 3-4), and neutropenia (40.6%, with 27.5% Grade 3-4).
• Notably, no cases of interstitial lung disease or ophthalmic toxicity, commonly associated with ADCs, were reported, and minimal GI toxicity was observed.
• The dose-limiting toxicity was myelosuppression, which was reversible.

Pharmacokinetics (PK) and Dose Optimization:

• The PK of CBX-12 and exatecan exhibited linear dose-proportional behavior, with a mean half-life ranging from 14 to 22 hours across the dose range studied. Two doses, 100 mg/m² and 125 mg/m², every 21 days are being studied in an ongoing Phase 2 trial, supporting further dose optimization to balance safety and efficacy in future studies.

The promising Phase 1 data provides strong validation for Cybrexa’s alphalex™ Platform, which enables multiple opportunities for value creation as Cybrexa deepens its efforts in oncology.  This foundational science has enabled the rapid advancement of CBX-12 into a recently initiated Phase 2 study in platinum-resistant ovarian cancer. An additional Phase 2 study in colorectal cancer is planned for 2025 in collaboration with the National Cancer Institute (NCI), as well as other Phase 2 studies in solid tumors as a monotherapy and in combination. CBX-15 is also being developed for solid tumors and is expected to be in the clinic in 2025 utilizing MMAE as the warhead.

About CBX-12

CBX-12 is a clinical-stage, first-in-class peptide drug conjugate (PDC) that utilizes Cybrexa’s proprietary alphalex™ technology to enhance delivery of exatecan to tumor cells and is composed of a pH-Low Insertion Peptide (pHLIP®), a linker, and exatecan. CBX-12 is designed to increase the efficacy and reduce the toxicity of topoisomerase I inhibition by delivering exatecan, a highly potent, second-generation topoisomerase I inhibitor, directly to the tumor cells. As an antigen-independent therapy, CBX-12 may have broad utility in patients who are not eligible for antigen-targeted therapies, including monoclonal antibodies and antibody-drug conjugates (ADCs), and has potential for use in combination regimens with other anti-cancer agents and immunotherapies.

About the alphalex™ Technology Platform

The Cybrexa alphalex technology is a novel antigen-independent, peptide-drug conjugate (PDC) platform that enables targeted delivery of highly potent anti-cancer treatments and aims to revolutionize the standard of care in oncology. The platform consists of a pH-Low Insertion Peptide (pHLIP®), a linker, and a small molecule anti-cancer agent. pHLIP peptides are a family of pH-low insertion peptides that target acidic cell surfaces. pHLIP was developed at Yale University and the University of Rhode Island and is exclusively licensed to pHLIP, Inc., and Cybrexa is a sublicensee of pHLIP, Inc.

About Cybrexa Therapeutics

Cybrexa is a privately held clinical-stage biotechnology company pioneering novel antigen-independent, tumor-targeting peptide drug conjugate (PDC) therapeutics. The company is led by a dynamic team of highly successful life science entrepreneurs and veteran drug development scientists. Cybrexa is on a mission to create therapeutics that revolutionize the standard of care in oncology, and its robust pipeline aims to combat breast, ovarian, non-small cell lung cancer, and a range of other tumors. Its assets are built on Cybrexa’s alphalex™ technology platform, which enables intracellular delivery of highly potent anti-cancer treatments.  Cybrexa is based in New Haven, Connecticut and was founded in 2017. For more information, please visit www.cybrexa.com or follow us on LinkedIn and X.

Investor Contact:
Per Hellsund, CEO, Cybrexa Therapeutics
860-799-1517
[email protected]

Media Contact:
Robin Fastenau, Scient PR
[email protected]

Industry Leader John Maraganore, Ph.D., Joins Cybrexa Therapeutics as Strategic Advisor

NEW HAVEN, Conn., June 25, 2024— Cybrexa Therapeutics, a clinical-stage oncology biotechnology company developing a novel class of tumor-targeting peptide drug conjugate (PDC) therapeutics, today announced that John Maraganore, Ph.D., has joined as a Strategic Advisor to the Company’s Executive Leadership Team. In this role, Dr. Maraganore will provide strategic guidance and leverage his extensive experience in the biotech industry to support the advancement of our alphalex™ technology platform, including progressing our lead candidate, a first-in-class peptide drug conjugate, CBX-12, (alphalex – exatecan) into Phase 2 ovarian cancer clinical trials, in the coming months. 

“This strategic appointment underscores our unwavering dedication to growth and innovation, and we are thrilled to have John join us at such an exciting time,” said Per Hellsund, President and CEO, Cybrexa. “As we prepare for our next important milestones, we are confident John’s insights and deep industry experience will propel the Company and the alphalex technology platform forward.” 

“Cybrexa’s innovative approach, leveraging pH in the tumor microenvironment to selectively kill cancer tissue while sparing healthy tissue, has the capability to revolutionize cancer treatment,” said Dr. John Maraganore. “The alphalex platform’s unique attributes, combined with the Company’s commitment to developing novel treatment options for patients, align perfectly with my own dedication to advance groundbreaking therapies for patients. I am particularly encouraged to see the recent efficacy and safety data from CBX-12’s Phase 1 trial, which showed activity in six different tumor types. I am excited to be part of this potentially transformative journey.” 

Dr. Maraganore served as the founding CEO and a Director of Alnylam Pharmaceuticals from 2002 to 2021, where he spearheaded the company’s growth from early-stage RNA interference (RNAi) research to the global approval and commercialization of their first four RNAi therapeutics. Under his leadership, the Company’s market capitalization value reached $25 billion, and he forged more than 20 major strategic pharmaceutical alliances. Before Alnylam, he was at Millennium Pharmaceuticals, Inc., where he oversaw the Company’s product franchises in oncology, cardiovascular, inflammatory and metabolic diseases, in addition to holding leadership roles in M&A, strategy, and biotherapeutics. He earned his M.S. and Ph.D. in biochemistry and molecular biology at the University of Chicago. Currently, he is a Venture Partner at ARCH Venture Partners, a Venture Advisor at Atlas Ventures, and a Senior Advisor for Blackstone Life Science. Beyond his venture capital roles, Dr. Maraganore serves on the boards of several privately held and public companies, as well as foundations. 

About CBX-12 

CBX-12 is a clinical-stage, first-in-class peptide drug conjugate (PDC) that utilizes Cybrexa’s proprietary alphalex™ technology to enhance delivery of exatecan to tumor cells and is composed of a pH-Low Insertion Peptide (pHLIP®), a linker and exatecan. CBX-12 is designed to increase the efficacy and reduce the toxicity of topoisomerase I inhibition by delivering exatecan, a highly potent, second-generation topoisomerase I inhibitor, directly to the tumor cells. As an antigen-independent therapy, CBX-12 may have broad utility in patients who are not eligible for antigen-targeted therapies, including monoclonal antibodies and antibody-drug conjugates (ADCs), and has potential for use in combination regimens with other anti-cancer agents and immunotherapies. Data from the ongoing Phase 1 trial of CBX-12 in patients with metastatic solid tumors demonstrated preliminary anti-tumor activity in a heavily pretreated patient population with a favorable safety profile. 

About the alphalex™ Technology Platform 

The Cybrexa alphalex™ technology is a novel antigen-independent, peptide-drug conjugate (PDC) platform that enables targeted delivery of highly potent anticancer treatments and aims to revolutionize the standard of care in oncology. The platform consists of a pH-Low Insertion Peptides (pHLIPs®) peptide, linker, and small molecule anti-cancer agent. pHLIP peptides are a family of pH-Low Insertion Peptides that target acidic cell surfaces. pHLIP was developed at Yale University and the University of Rhode Island, and is exclusively licensed to pHLIP, Inc., and Cybrexa is a sublicensee of pHLIP, Inc. To date the alphalex platform has generated three programs at Cybrexa; CBX-12, CBX-13 and CBX-15. 

About Cybrexa 

Cybrexa is a privately held clinical-stage biotechnology company pioneering novel antigen-independent tumor-targeting peptide drug conjugate (PDC) therapeutics. The company is led by a dynamic team of highly successful life science entrepreneurs and veteran drug development scientists. It is on a mission to create therapeutics that revolutionize the standard of care in oncology. Cybrexa’s robust pipeline aims to combat breast cancer, ovarian cancer, non-small cell lung cancer, colorectal cancer and a range of other tumors. Its assets are built on Cybrexa’s alphalex™ technology platform, which enables intracellular delivery of highly potent anticancer treatments. Cybrexa is based in New Haven, Conn. and was founded in 2017. For more information about Cybrexa, please visit www.cybrexa.com or follow us on LinkedIn and Twitter. 

Investor Contact: 

Per Hellsund, CEO, Cybrexa Therapeutics
860-799-1517
[email protected] 

Media Contact: 

Tara DiMilia, TellMed Strategies
908-884-7024
[email protected]