San Diego, CA, May 18, 2026 — Biotheryx, Inc., a biopharmaceutical company focused on the discovery and development of first-in-class protein degraders for cancer and inflammatory diseases, today announced the data from its first-in-human Phase 1 Dose Escalation study evaluating BTX-9341, a novel CDK4/6 bifunctional degrader, as monotherapy and in combination with fulvestrant in participants with advanced/metastatic HR+/HER2- breast cancer who received prior CDK4/6 inhibitor therapy. The Phase 1 Dose Expansion portion of the study is currently ongoing.

“BTX-9341 has a highly favorable safety profile, with no clear evidence of key class related toxicities of other CDK4/6 inhibitors including gastrointestinal toxicities (diarrhea, nausea, vomiting), hepatotoxicity and prolongation of the QTc interval,” said Dr. Rachel M Layman, MD (Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center). “The drug shows encouraging clinical activity in a heavily pretreated patient population in the post-CDK4/6 inhibitor setting and shows compelling evidence of the importance of targeting CDK2/4/6 to address multiple resistance pathways.”

Data from the Phase 1 Dose Escalation study demonstrate evidence of clinical activity, including prolonged partial response and stable disease in a heavily pretreated patient population. Pharmacokinetic analyses showed BTX-9341 exposures consistent with target engagement concentrations. Importantly, BTX-9341 was well tolerated, with participants on treatment for over 12 cycles (48 weeks), including on monotherapy and in combination with fulvestrant. Adverse events were mild to moderate and easily manageable.

Key Highlights from Dose Escalation Portion of the Phase 1 Study

• Favorable safety and tolerability profile with no serious adverse events or treatment discontinuations due to adverse events in all participants (N=28). Hematologic adverse events were transient and reversible. There were no ≥ Grade 3 non-hematologic events.
• Approximate dose-proportional pharmacokinetics supporting once-daily dosing.
• Clinical activity was observed in a heavily pretreated patient population post-CDK4/6 inhibitors with up to 6 prior lines of therapy in the metastatic setting; approximately 40% and 36% of participants had received chemotherapy and PI3K/AKT/mTOR or other targeted therapies, respectively. Clinical Benefit Rates¹ (CBRs) of 41.7% and 80% were observed in treatment-evaluable participants² (n=24), and participants representative of the dose expansion criteria (n=10), respectively.
• Target engagement consistent with CDK4/6 degradation mechanism based on a significant reduction in serum Thymidine Kinase activity, and reductions in the levels of CDK4, CDK6, and CDK2 in peripheral blood mononuclear cells (PBMCs). This is consistent with BTX-9341’s unique ability to address multiple convergent resistance mechanisms to CDK4/6 inhibitor therapies by degrading CDK4/6 and inhibiting downstream transcription of CDK2.
• The study is still ongoing with multiple participants remaining on treatment for 12 to >18 cycles. The data are as of May 6, 2026.

“These encouraging clinical results mark an important milestone for our Phase 1 study evaluating BTX-9341, a first-in-class CDK4/6 bifunctional degrader,” said Dr. Leah Fung, CEO of Biotheryx. “BTX-9341 has demonstrated a promising safety and tolerability profile, along with early signs of clinical activity in participants whose disease progressed following prior CDK4/6 inhibitor therapy. Given that CDK6 upregulation and Cyclin E amplification are established mechanisms of resistance to CDK4/6 inhibitors, these findings highlight the importance of degrading CDK4/6 and inhibiting downstream transcription of CDK2 to address convergent resistance mechanisms and may redefine the post-CDK4/6 inhibitor setting in advanced/metastatic HR+/HER2- breast cancer.”

Advancing to Dose Expansion

Based on these findings, the company is continuing with its Phase 1 Dose Expansion portion of the trial. The expansion cohorts have begun enrolling participants and will further evaluate the efficacy and safety of BTX-9341 in combination with fulvestrant and will build on the safety, tolerability, pharmacokinetics and pharmacodynamic activity of BTX-9341 established in the Dose Escalation phase. The trial is being conducted at multiple sites in the United States and is expected to enroll up to 78 participants across two treatment arms based on the recommended dose identified in the earlier Dose Escalation phase. The primary endpoint of this study is the Overall Response Rate (ORR), with key secondary endpoints including the measurement of investigator-assessed Clinical Benefit Rate (CBR) and Progression Free Survival (PFS).

About BTX-9341

BTX-9341 is a first-in-class, oral degrader of CDK4/6, important targets for a range of cancers and clinically validated in HR+/HER2- breast cancer. In preclinical breast cancer models, BTX-9341 demonstrated enhanced activity compared with CDK4-only and CDK4/6 inhibitors through potent and highly selective catalytic degradation of CDK4 and CDK6, robust inhibition of CDK2 transcription, cell cycle arrest, and ultimately superior in vivo efficacy in breast cancer xenografts. Beyond this increased efficacy potential, BTX-9341 is differentiated from CDK4-only and CDK4/6 inhibitor approaches through the ability to overcome key resistance mechanisms that can limit the impact of inhibitors in second line HR+/HER2- metastatic breast cancer.

About Biotheryx

Biotheryx is a clinical-stage, biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including molecular glues and bifunctional degraders. Members of our founding and scientific teams previously developed the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation. We have applied our expertise in Cereblon modulation to build our proprietary PRODEGY platform and pipeline of protein degraders for oncology and inflammatory diseases. Our approach deploys molecular glues to target undruggable proteins and bifunctional degraders to target validated proteins that conventional strategies, like protein inhibition, have insufficiently addressed. The Biotheryx pipeline includes BTX-9341, a first-in-class, oral, CDK4/6 bifunctional degrader that inhibits the transcription of CDK2 and Cyclin E and is being tested in a first-in-human Dose Optimization clinical study in HR+/HER2- breast cancer participants who have progressed on CDK4/6 inhibitor therapy. Our pre-clinical pipeline advances undisclosed bifunctional degraders and molecular glues, including degraders as payloads for antibody drug conjugation. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements. All statements other than statements of historical facts contained in this press release, including statements regarding the Company’s strategy, future operations, research and development, planned and ongoing clinical trials, the timing and likelihood of regulatory filings and approvals for the Company’s product candidates, anticipated benefits, characteristics and attributes of the Company’s compounds and programs, the Company’s ability to commercialize its product candidates, the potential benefits of collaborations, and prospects, plans and objectives of management, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “milestone,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on the Company’s current expectations and projections about future events and financial trends that the Company believes may affect its financial condition, results of operations, business strategy and financial needs. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements. Although the Company believes that it has a reasonable basis for these forward-looking statements, these forward-looking statements are subject to a number of known and unknown risks, uncertainties and assumptions and the Company cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur at all. The actual results may differ materially from those expressed or implied by these forward-looking statements. Except as required by law, the Company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.

1. Clinical Benefit Rate (CBR), participant on treatment for up to 24 weeks (+/-7 days)
2. Treatment-evaluable participant, participant on treatment for at least one cycle with one post-baseline scan after Cycle 1.

Contacts:

Biotheryx Investors/Media
David Pieters
[email protected]

SAN DIEGO, CA, May 4, 2026 – Biotheryx, Inc., a biopharmaceutical company focused on the discovery and development of first-in-class protein degraders for cancer and inflammatory diseases, today announced that data from its Phase 1A Dose Escalation Study of BTX-9341, a potent and selective CDK4/6 degrader, in combination with fulvestrant for the treatment of HR+/HER2- breast cancer in patients who have previously received CDK4/6 inhibitor therapy in the advanced and/or metastatic setting, will be presented as an oral presentation at the 2026 European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress, taking place May 6 – 8 in Berlin, Germany.

2026 ESMO Breast Cancer Presentation Details:

Title: Dose optimization of BTX-9341, a first-in-class CDK4/6 bifunctional degrader, in CDK4/6 inhibitor-pretreated HR+/HER2− advanced/metastatic breast cancer

Presenter: Dr. Matthew Goetz, MD, Mayo Clinic, Rochester, USA

Presentation #: 421RO

Session: Rapid Oral Session 2, Berlin Hall

Session Date and Time: Friday, May 8, 2026 | 8:30-10:00 AM

About BTX-9341

BTX-9341 is a first-in-class, oral degrader of CDK4/6, important targets for a range of cancers and clinically validated in HR+/HER2- breast cancer. In preclinical breast cancer models, BTX-9341 demonstrated superiority to CDK4/6 inhibitors through potent and highly selective catalytic degradation of CDK4 and CDK6, robust inhibition of CDK2 and Cyclin E transcription, cell cycle arrest, and ultimately superior in vivo efficacy in breast cancer xenografts. Beyond this increased efficacy potential, BTX-9341 is differentiated from CDK4/6 inhibitor approaches through the ability to overcome key resistance mechanisms that limit the impact of inhibitors in second line HR+/HER2- metastatic breast cancer.

About Biotheryx, Inc.

Biotheryx is a clinical-stage, biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including molecular glues and bifunctional degraders. Members of our founding and scientific teams previously developed the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation. We have applied our expertise in Cereblon modulation to build our proprietary PRODEGY platform and pipeline of protein degraders for oncology and inflammatory diseases. Our approach deploys molecular glues to target undruggable proteins and bifunctional degraders to target validated proteins that conventional strategies, like protein inhibition, have insufficiently addressed. The Biotheryx pipeline includes BTX-9341, a first-in-class, oral, CDK4/6 bifunctional degrader that inhibits the transcription of CDK2 and Cyclin E, in first-in-human dose escalation and optimization clinical study in HR+/HER2- breast cancer patients who have progressed on CDK4/6 inhibitor therapy. Our pre-clinical pipeline advances undisclosed bifunctional degraders and molecular glues, including degraders as payloads for antibody drug conjugation. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Biotheryx Investors/Media
David Pieters
[email protected]

SAN DIEGO, CA, March 18, 2026 – Biotheryx, Inc., a biopharmaceutical company focused on the discovery and development of first-in-class protein degraders for cancer and inflammatory diseases, today announced that the first patient has been dosed in the dose expansion phase of its clinical trial evaluating BTX-9341, a potent and selective CDK4/6 degrader, in combination with fulvestrant for the treatment of HR+/HER2- breast cancer in patients who have previously received CDK4/6 inhibitor therapy in the advanced and/or metastatic setting.

The dose expansion portion of the trial is a randomized study designed to evaluate the efficacy and safety of BTX-9341 in combination with fulvestrant. The trial is being conducted at multiple sites in the United States and is expected to enroll approximately 80 patients across two treatment arms based on the recommended dose identified in the earlier dose escalation phase. This dose expansion study builds on the recently completed dose escalation phase that evaluated the safety, tolerability, pharmacokinetics and pharmacodynamic activity of BTX-9341. The primary endpoint of this study is the Overall Response Rate (ORR), with key secondary endpoints including the measurement of investigator-assessed Clinical Benefit Rate (CBR) and Progression Free Survival (PFS).

“We are pleased to have dosed the first patient in the dose expansion portion of our clinical trial evaluating BTX-9341 in combination with fulvestrant.” said Dr. Leah Fung, Chief Executive Officer of Biotheryx. “The encouraging safety, pharmacokinetics, and preliminary activity observed in the earlier dose escalation portion of the study support advancing BTX-9341 into this next stage of clinical evaluation. We believe the differentiated mechanism of targeted CDK4/6 degradation has the potential to address resistance seen with currently available CDK4/6 inhibitors, and we look forward to further assessing BTX-9341 in combination with fulvestrant to improve outcomes for patients with HR+/HER2- breast cancer who have previously received CDK4/6 inhibitor therapy.”

About BTX-9341

BTX-9341 is a first-in-class, oral degrader of CDK4/6, important targets for a range of cancers and clinically validated in HR+/HER2- breast cancer. In preclinical breast cancer models, BTX-9341 demonstrated superiority to CDK4/6 inhibitors through potent and highly selective catalytic degradation of CDK4 and CDK6, robust inhibition of CDK2 and Cyclin E transcription, cell cycle arrest, and ultimately superior in vivo efficacy in breast cancer xenografts. Beyond this increased efficacy potential, BTX-9341 is differentiated from CDK4/6 inhibitor approaches through the ability to overcome key resistance mechanisms that limit the impact of inhibitors in second line HR+/HER2- metastatic breast cancer.

About Biotheryx, Inc.

Biotheryx is a clinical-stage, biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including molecular glues and bifunctional degraders. Members of our founding and scientific teams previously developed the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation. We have applied our expertise in Cereblon modulation to build our proprietary PRODEGY platform and pipeline of protein degraders for oncology and inflammatory diseases. Our approach deploys molecular glues to target undruggable proteins and bifunctional degraders to target validated proteins that conventional strategies, like protein inhibition, have insufficiently addressed. The Biotheryx pipeline includes BTX-9341, a first-in-class, oral, CDK4/6 bifunctional degrader that inhibits the transcription of CDK2 and Cyclin E, in first-in-human dose escalation and optimization clinical study in HR+/HER2- breast cancer patients who have progressed on CDK4/6 inhibitor therapy. Our pre-clinical pipeline advances undisclosed bifunctional degraders and molecular glues, including degraders as payloads for antibody drug conjugation. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Biotheryx Investors/Media
David Pieters
[email protected]

Topline data readout from Phase 1a clinical trial expected in Q1 2026

SAN DIEGO, CA, November 17, 2025 – Biotheryx, Inc., a biopharmaceutical company focused on the discovery and development of first-in-class protein degraders for cancer and inflammatory diseases, today announced the completion of enrollment in the ongoing Phase 1a clinical trial of BTX-9341, a potent and selective CDK4/6 degrader, for the treatment of advanced and/or metastatic HR+/HER2- breast cancer in patients who have previously received CDK4/6 inhibitor therapy either in the adjuvant or metastatic setting.

The Phase 1a clinical trial began with dose escalation of BTX-9341 as a monotherapy, followed by a combination with fulvestrant. The primary objective of the Phase 1a trial is to assess safety, tolerability, pharmacokinetic and pharmacodynamic activity of BTX-9341 as a monotherapy and in combination with fulvestrant. Based on the recommended dose from Phase 1a, there will be a formal evaluation of efficacy in the dose expansion phase of the trial.

“Completing enrollment in the Phase 1a trial for BTX-9341 marks a significant step forward in advancing a very promising first-in-class treatment option for patients with HR+/HER2- breast cancer who have received prior CDK4/6 inhibitor therapy.” said Dr. Leah Fung, Chief Executive Officer of Biotheryx. “We are deeply grateful to the patients, investigators, and our team who made this possible as we continue to work together towards the common goal of improving patient lives.”

About BTX-9341

BTX-9341 is a first-in-class, oral degrader of CDK4/6, important targets for a range of cancers and clinically validated in HR+/HER2- breast cancer. In preclinical breast cancer models, BTX-9341 demonstrated superiority to CDK4/6 inhibitors through potent and highly selective catalytic degradation of CDK4 and CDK6, robust inhibition of Cyclin E and CDK2 transcription, cell cycle arrest and ultimately superior in vivo efficacy in breast cancer xenografts. Beyond this increased efficacy potential, BTX-9341 is differentiated from CDK4/6 inhibitor approaches through the ability to overcome key resistance mechanisms that limit the impact of inhibitors in second line HR+/HER2- breast cancer.

About Biotheryx, Inc.

Biotheryx is a clinical-stage, biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including molecular glues and bifunctional degraders. Members of our founding and scientific teams previously developed the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation. We have applied our expertise in Cereblon modulation to build our proprietary PRODEGY platform and pipeline of protein degraders for oncology and inflammatory diseases. Our approach deploys molecular glues to target undruggable proteins and bifunctional degraders to target validated proteins that conventional strategies, like protein inhibition, have insufficiently addressed. The Biotheryx pipeline includes BTX-9341, a first-in-class, oral, CDK4/6 bifunctional degrader that inhibits the transcription of CDK2 and Cyclin E, in FIH Phase 1a clinical studies in HR+/HER2- breast cancer patients who have progressed on CDK4/6 inhibitor therapy. Our pre-clinical pipeline advances undisclosed bifunctional degraders and molecular glues, including degraders as payloads for antibody drug conjugation. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Biotheryx Investors/Media
David Pieters
[email protected]

Partnership will continue to leverage Biotheryx’s PRODEGY platform to discover molecular glue degraders for multiple historically undruggable novel targets

Biotheryx will receive an undisclosed upfront payment and is eligible to receive up to $354 million in potential downstream milestone payments for each target plus royalties on net sales

SAN DIEGO, CA, June 23, 2025 – Biotheryx, Inc., a biopharmaceutical company focused on the discovery and development of first-in-class protein degraders for cancer and inflammatory diseases, today announced it has entered into a second Research Collaboration and License agreement with Incyte to discover and develop molecular glue degraders for novel oncology targets. At the same time, Incyte triggered an additional target under the terms of the first agreement.

“We are excited to expand our collaboration with Incyte to discover molecular glue degraders for novel targets. Biotheryx and Incyte are united in the mission to deliver groundbreaking therapies,” said Dr. Leah Fung, Chief Executive Officer of Biotheryx. “Biotheryx’s PRODEGY platform features our Cereblon-directed chemical library designed to identify novel neosubstrates and discover molecular glues that enable the degradation of previously undruggable proteins. In this broadened partnership with Incyte, we will continue to leverage our proven approach for neosubstrate and molecular glue discovery with potential to unlock innovative protein degrader therapies.”

Under the terms of the agreement, Biotheryx will utilize its distinctive PRODEGY platform to analyze multiple historically undruggable targets to identify proteins that are potential neosubstrates of Cereblon. Biotheryx will also grant Incyte access to the PRODEGY chemical library and Incyte will be responsible for screening the library against multiple targets to identify and discover novel molecular glue degraders. In return, Biotheryx will receive an undisclosed upfront payment for technology and library access. Biotheryx is also eligible to receive up to $354 million in potential fees and future milestone payments plus tiered single-digit royalties on global net product sales for each target. Additionally, under the terms of the agreement, Incyte will be solely responsible for the discovery, development and commercialization of any molecular glue degraders under the collaboration. Further details related to the collaboration structure and financial terms of the deal were not disclosed.

“We look forward to growing our collaboration with Biotheryx through this additional agreement, and to combining our expertise to accelerate the identification of new targets as we work toward the discovery and development of innovative therapies for patients,” said Patrick Mayes, Ph.D., Group Vice President, Biology at Incyte.

About Biotheryx, Inc.

Biotheryx is a clinical-stage, biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including molecular glues and bifunctional degraders. Members of our founding and scientific teams previously developed the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation. We have applied our expertise in Cereblon modulation to build our proprietary PRODEGY platform and pipeline of protein degraders for oncology and inflammatory diseases. Our approach deploys molecular glues to target undruggable proteins and bifunctional degraders to target validated proteins that conventional strategies, like protein inhibition, have insufficiently addressed. The Biotheryx pipeline includes BTX-9341, a first-in-class, oral, CDK4/6 bifunctional degrader that inhibits the transcription of CDK2 and Cyclin E, in FIH Phase 1a clinical studies in HR+/HER2- breast cancer patients who have progressed on CDK4/6 inhibitor therapy. Our pre-clinical pipeline advances undisclosed bifunctional degraders and molecular glues, including degraders as payloads for antibody drug conjugation. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Biotheryx Investors/Media
David Pieters
[email protected]

SAN DIEGO, CA. July 17, 2024 — Biotheryx, Inc., a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders with a focus on validated targets in cancer and inflammatory diseases, today announced that the first patient has been dosed in its Phase 1 clinical trial evaluating BTX-9341, an investigational oral and bifunctional degrader of cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6), as a monotherapy and in combination with fulvestrant for patients with advanced and/or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer who have previously received CDK4/6 inhibitor therapy either in the adjuvant or metastatic setting.

“BTX-9341 is a potent and selective CDK4/6 degrader that has shown significant anti-tumor activity in both CDK4/6 inhibitor naïve and resistant preclinical models. We are optimistic that it will meet a critical unmet medical need for patients with HR+/HER2- breast cancer who have received prior CDK4/6 inhibitor therapy,” said Leah Fung, Ph.D., CEO of Biotheryx. “Dosing the first patient in this trial represents a significant milestone for Biotheryx, the patients we aim to serve and the scientists who have made this possible.”

The Phase 1 clinical trial will begin with dose escalation of BTX-9341 as a monotherapy, followed by a combination with fulvestrant and will conclude with dose expansion of BTX-9341 in combination with fulvestrant. The trial will assess safety, tolerability, pharmacokinetic and pharmacodynamic activity of BTX-9341 as a monotherapy and in combination with fulvestrant. Once the recommended Phase 2 dose of the combination has been determined, there will be a formal evaluation of efficacy in an expansion cohort.

“We are thrilled to have dosed the first patient with BTX-9341 at The START Center for Cancer Research,” stated START Co-Founder and Co-Director of Clinical Research, Dr. Amita Patnaik, MD, FRCPC. “BTX-9341 is a highly novel, first-in-class, potent and selective degrader of CDK4/6, representing an innovative therapeutic approach. It has the potential to transform the care of patients with advanced and/or metastatic HR+/HER2- breast cancer, particularly those who have received prior CDK4/6 inhibitor therapies. This milestone is perfectly aligned with START’s mission to accelerate drug development and provide early access to cutting-edge anticancer therapies, bringing hope to patients and their families.”

In preclinical studies, orally administered BTX-9341 demonstrated in vivo CDK4/6 degradation and improved anti-tumor activity as a monotherapy compared to current standard of care treatment regimens. BTX-9341 also demonstrated synergies with selective estrogen receptor degraders including fulvestrant, elacestrant and camizestrant in CDK4/6 naïve and resistant models.

About BTX-9341

BTX-9341 is a first-in-class, oral degrader of CDK4/6, important targets for a range of cancers and clinically validated in HR+/HER2- breast cancer. In preclinical breast cancer models, BTX-9341 demonstrated superiority to CDK4/6 inhibitors through potent and highly selective catalytic degradation of CDK4 and CDK6, robust inhibition of Cyclin E and CDK2 transcription, cell cycle arrest and ultimately superior in vivo efficacy in breast cancer xenografts. Beyond this increased efficacy potential, BTX-9341 is differentiated from CDK4/6 inhibitor approaches through the ability to overcome key resistance mechanisms that limit the impact of inhibitors in second line HR+/HER2- breast cancer.

About Biotheryx, Inc.

Biotheryx is a clinical-stage biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including bifunctional degraders and molecular glues. Our focus is on deploying the differentiated potential of degraders towards validated targets in cancer and inflammatory disease. Members of our founding and scientific teams previously developed the IMiDs, the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation, and we have applied our expertise in Cereblon binding to build our proprietary PRODEGY platform. Biotheryx’s clinical program, BTX-9341, a bifunctional degrader of CDK4 and CDK6, began a Phase 1 clinical trial in the third quarter of 2024. Biotheryx’s pipeline also includes BTX-10908, a first-in-class degrader of SOS1 for pan-KRAS mutant cancers and PDE4 degraders for inflammatory diseases. For more information, please visit biotheryx.com and engage with us on LinkedIn.

Biotheryx Contact

Sumitra Gupta
Director of Business Development and Strategy
[email protected]

SAN DIEGO, CA. May 7, 2024 — Biotheryx, Inc., a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders with a focus on validated targets in cancer and inflammatory disease, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for BTX-9341, a novel cyclin-dependent kinase 4/6 (CDK4/6) bifunctional degrader. The Company plans to initiate the Phase 1 clinical trial in the second half of 2024 and intends to enroll patients with HR+/HER2- breast cancer resistant to CDK4/6 inhibitor therapies.

“Securing FDA clearance for our BTX-9341 IND application marks a significant milestone for Biotheryx, affirming our commitment to advancing innovative, orally bioavailable targeted protein degraders. As we transition from promising preclinical data to clinical trials, we are poised to explore the potential of BTX-9341 in offering tangible clinical benefits to patients battling breast cancer,” said Leah Fung, Ph.D., CEO of Biotheryx.

The Phase 1 clinical trial includes dose escalation for the initial monotherapy administration of BTX-9341 and combination dose expansion combining BTX-9341 with fulvestrant. The initial clinical evaluation will be focused on safety, biological activity and preliminary efficacy.

About BTX-9341

BTX-9341 is a first-in-class, oral degrader of cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6), important targets for a range of cancers and clinically validated in the context of certain breast cancers. In preclinical breast cancer models, BTX-9341 demonstrated superiority to CDK4/6 inhibitors through potent and highly selective degradation of CDK4 and CDK6, robust inhibition of Cyclin E and CDK2 transcription, cell cycle arrest and ultimately superior in vivo efficacy in breast cancer xenografts. Beyond this increased efficacy potential, BTX-9341 is differentiated from CDK4/6 inhibitor approaches through the potential ability to overcome key resistance mechanisms that limit the impact of inhibitors (~20% of patients have intrinsic resistance and up to 70% have acquired resistance to CDK4/6 inhibitors) and significantly enhanced penetration of the blood-brain-barrier.

About Biotheryx, Inc.

Biotheryx is a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including bifunctional degraders and molecular glues. Our initial focus is on deploying the differentiated potential of degraders towards validated targets in cancer and inflammatory disease. Members of our founding and scientific teams previously developed the IMiDs, the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation, and we have applied our expertise in Cereblon binding to build our proprietary PRODEGY platform. Our pipeline of bifunctional degraders includes BTX-9341 for HR+/HER2- breast cancer, the first ever bifunctional degrader of CDK4 and CDK6 to receive IND approval from the FDA, as well as first-in-class degraders of SOS1 for pan-KRAS mutant cancers, and PDE4 for inflammatory diseases. For more information, please visit biotheryx.com and engage with us on LinkedIn.

Biotheryx Contact

Sumitra Gupta
Director of Business Development and Strategy
[email protected]

BTX-9341 demonstrated potent degradation of CDK4/6 and tumor growth regression in resistant cells in preclinical breast cancer models, along with robust blood brain barrier penetration

SOS1 degraders exhibited antiproliferative effects and inhibited tumor cell growth in a broad range of KRAS-mutated cell lines

SAN DIEGO, CA., May 25, 2023 — Biotheryx, Inc., a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders with a focus on validated targets in cancer and inflammatory disease, today announced two poster presentations at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, being held June 2–6, 2023, in Chicago, Illinois and online. The presentations highlight preclinical data for bifunctional degraders of CDK4/6, including development candidate BTX-9341, for the treatment of estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-), and of son of sevenless homolog 1 (SOS1) for the treatment of KRAS mutant cancers.

“These new preclinical data demonstrate the potential of our bifunctional CDK4/6 and SOS1 degraders to potently degrade their targets, ultimately effectively inhibiting tumor growth together with the strength of Biotheryx’s PRODEGY platform to efficiently design first-in-class degraders,” said Philippe Drouet, President and Chief Executive Officer of Biotheryx. “Besides these encouraging efficacy results, BTX-9341, our oral CDK4/6 development candidate, exhibited superior blood brain barrier penetration versus inhibitors and good tumor exposure when dosed orally. We look forward to advancing BTX-9341 towards clinical development to overcome drug resistance challenges faced by patients with solid tumors such as ER+/HER2- breast cancer.”

2023 ASCO Annual Meeting Presentation Details:

Title: Discovery of CDK4/6 bifunctional degraders for ER+/HER2- breast cancer and triple negative breast cancer
Presenter: Hannah Majeski, Ph.D., Principal Scientist – Biology
Abstract #: 1083
Session: Breast Cancer – Metastatic
Session Date and Time: Sunday, June 4, 2023, at 8:00 a.m. CDT

Highlights:

• CDK4/6 inhibitors are used to treat ER+/ HER2- breast cancer, but some patients have exhibited innate resistance, and many are shown to develop acquired resistance after three years on therapy.
• BTX-9341, discovered and developed by Biotheryx’s proprietary PRODEGY platform, is a potent, Cereblon- and proteasome-dependent degrader of CDK4 and CDK6 in multiple breast cancer cell lines.
• BTX-9341 demonstrated in vitro CDK4 and CDK6 degradation in multiple breast cancer cell lines and potent inhibition of cell proliferation. This potency was shown to be superior to CDK4/6 inhibitors, due to Cereblon-mediated target degradation.
• The CDK4/6 bifunctional degraders were active in a CDK4/6 inhibitor resistant cell line and in multiple PDX CDK4/6 inhibitor resistant organoid models.
• BTX-9341 exhibited good tumor exposure when dosed orally, and induced a dose-dependent reduction in CDK4, CDK6 and pRB levels in MCF7 xenograft tumors. This resulted in dose dependent tumor growth inhibition, tumor regression and superior efficacy compared to CDK4/6 inhibitors.
• BTX-9341 and its analogue bifunctional degraders have also shown blood brain barrier penetration and superior inhibition of tumor growth in an MCF7 intracranial mouse model compared to a CDK4/6 inhibitor.
• The combination of the enhanced efficacy, activity in CDK4/6 inhibitor resistant models and blood brain barrier penetration demonstrate the potential for CDK4/6 degraders in a range of potential cancer indications.
  

Title: Development of bifunctional CRBN-SOS1 degraders for treatment of mutant KRAS cancers
Presenter: Kyle Begovich, Ph.D., Senior Scientist – Biology
Abstract #: 3151
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Session Date and Time: Saturday, June 3, 2023, at 8:00 a.m. CDT

Highlights:

• KRAS is the most frequently mutated cancer-causing oncogene and is mutated in over 20% of all human cancers, including an estimated 90% of pancreatic cancer, 45% of colorectal cancer and 30% of lung cancer. Combination therapeutic approaches are likely needed to avoid drug resistance in the treatment of KRAS mutant cancers, such as coupling KRAS inhibition with a blockade of its guanine exchange factor (GEF), SOS1, to keep KRAS in its inactive state as well as prevent upstream pathway reactivation.
• Biotheryx’s SOS1 bifunctional degraders demonstrated antiproliferative effects across a range of KRAS-mutant cell lines. Treatment with SOS1 degraders in KRAS-mutant xenograft models resulted in greater than 90% degradation of SOS1 in tumors and subsequently led to significant tumor growth inhibition as a single agent.
• SOS1 degraders also exhibited synergistic effects with other RAS/MAPK pathway inhibitors, such as KRAS G12C, KRASG12D, EGFR and MEK inhibitors in in vitro studies as well as in KRAS-mutant xenograft models.
• These data support the potential of SOS1 degradation as a valuable treatment option for a range of KRAS mutant cancers, as a monotherapy and in combination with other RAS-MAPK pathway inhibitors.

Following the presentations at the meeting, PDF copies of the presentations and posters will be available in the “Publications and Presentations” section of Biotheryx’s website.

About Biotheryx, Inc.

Biotheryx is a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including bifunctional degraders and molecular glues. Our initial focus is on deploying the differentiated potential of degraders towards validated targets in cancer and inflammatory disease. Members of our founding and scientific teams previously developed the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation, and we have applied our expertise in Cereblon binding to build our proprietary PRODEGY platform. Our pipeline of bifunctional degraders includes BTX-9341, the first-ever degrader of CDK4/6 for solid tumors, and the first-ever degraders of SOS1 for pan-KRAS mutant cancers and PDE4 for inflammatory diseases. Our pipeline of molecular glues includes BTX-1188, a rationally designed, dual-targeting molecular glue degrader of GSPT1 and IKZF1/3 for acute myeloid leukemia and solid tumors, and undisclosed oncology targets through our research collaboration and license agreement with Incyte. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Investors/Media
Argot Partners
212.600.1902
[email protected]

Data for CDK4/6 and SOS1 programs highlight differentiated therapeutic profiles

BTX-9341 nominated as development candidate for CDK4/6 degrader program for the treatment of solid tumors, currently in IND-enabling studies

SAN DIEGO, CA., April 17, 2023 — Biotheryx, Inc., a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders with a focus on validated targets in cancer and inflammatory disease, today announced data presentations on two first-in-class programs at the American Association for Cancer Research (AACR) 2023 Annual Meeting held in Orlando, Florida, on April 14–19, 2023. The presentations highlight preclinical data for bifunctional degraders of cyclin-dependent kinase (CDK) 4/6 for the treatment of solid tumors, and bifunctional degraders of son of sevenless homolog 1 (SOS1) for the treatment of KRAS mutant cancers. Additionally, the Company has nominated BTX-9341 as a development candidate for the CDK4/6 degrader program and has commenced IND-enabling studies.

“Biotheryx is advancing first-in-class bifunctional degraders developed through our PRODEGY platform to overcome common resistance mechanisms to existing inhibitors and provide differentiated treatment possibilities for people facing cancer,” said Philippe Drouet, President and Chief Executive Officer of Biotheryx. “At AACR, we are proud to share encouraging preclinical data that highlights the potential of these exciting programs. BTX-9341, our oral CDK4/6 development candidate, has demonstrated superior efficacy in preclinical models of ER+/HER2- breast cancer when compared to CDK4/6 inhibitors, superior blood-brain-barrier penetration while importantly also showing the ability to be effective in models resistant to existing CDK4/6 inhibitors. Similarly, in preclinical KRAS mutant cancer models, our SOS1 degraders resulted in greater than 90% degradation of SOS1 in tumors and led to significant tumor growth inhibition.”

AACR 2023 Presentation Details:

Title: Discovery of CDK4/6 bifunctional degraders for ER+/HER2- breast cancer and triple negative breast cancer
Presenter: Hannah Majeski, Ph.D., Principal Scientist – Biology
Abstract #: 1553
Session: Cell Cycle/Cell Proliferation Inhibitors for Cancer Therapy
Session Date and Time: Monday, April 17, 2023, at 9:00 a.m. ET
Highlights:

• CDK4/6 inhibitors are used to treat estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer, but some patients have exhibited innate resistance, and many are shown to develop acquired resistance after three years on therapy.
• Biotheryx’s CDK4/6 bifunctional degraders demonstrated in vitro CDK4 and CDK6 degradation in multiple breast cancer cell lines and potent inhibition of cell proliferation. This potency was shown to be superior to CDK4/6 inhibitors and due to Cereblon-mediated target degradation.
• CDK4/6 bifunctional degraders were active in a CDK4/6 inhibitor resistant cell line and in multiple PDX CDK4/6 inhibitor resistant organoid models.
• CDK4/6 bifunctional degraders exhibited good tumor exposure when dosed orally, and induced a dose-dependent reduction in CDK4, CDK6, and pRB levels in MCF7 xenograft tumors. This resulted in dose dependent tumor growth inhibition and superior efficacy compared to CDK4/6 inhibitors.
• These degraders have also shown blood brain barrier penetration and superior inhibition of tumor growth in an MCF7 intracranial mouse model compared to a CDK4/6 inhibitor.
• The combination of the enhanced efficacy, activity in resistant cell lines and blood brain barrier penetration demonstrate the potential for CDK4/6 degraders in a range of potential cancer indications.

Title: Development of bifunctional CRBN-SOS1 degraders for treatment of mutant KRAS cancers
Presenter: Kyle Begovich, Ph.D., Senior Scientist – Biology
Abstract #: 1578
Session: New Therapeutic Targeted Agents
Session Date and Time: Monday, April 17, 2023, at 9:00 a.m. ET
Highlights:

• KRAS is the most frequently mutated cancer-causing oncogene and is mutated in over 20% of all human cancers, including an estimated 90% of pancreatic tumors and 45% of colorectal tumors. Combinational therapeutic approaches are needed to avoid drug resistance in the treatment of KRAS mutant cancers, such as coupling KRAS inhibition with a blockade of its guanine exchange factor (GEF), SOS1, to keep KRAS in its inactive state as well as prevent upstream pathway reactivation.
• Biotheryx SOS1 degraders demonstrated antiproliferative effects across a range of KRAS-mutated cell lines. Consistent with this notion, treatment with SOS1 degraders in KRAS-mutant xenograft models resulted in greater than 90% degradation of SOS1 in tumors and subsequently led to significant tumor growth inhibition as a single agent.
• SOS1 degraders also exhibited synergistic effects with other RAS/MAPK inhibitors in in vitro studies as well as KRAS-mutant xenograft models.
• These data support the potential of SOS1 degradation as a valuable treatment option for a range of KRAS mutant cancers.

Following the presentations at the meeting, PDF copies of the presentations and posters will be available in the “Publications and Presentations” section of Biotheryx’s website.

About Biotheryx, Inc.

Biotheryx is a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including bifunctional degraders and molecular glues. Our initial focus is on deploying the differentiated potential of degraders towards validated targets in cancer and inflammatory disease. Members of our founding and scientific teams previously developed the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation, and we have applied our expertise in Cereblon binding to build our proprietary PRODEGY platform. Our pipeline of bifunctional degraders includes BTX-9341, the first-ever degrader of CDK4/6 for solid tumors, and the first-ever degraders of SOS1 for pan-KRAS mutant cancers and PDE4 for inflammatory diseases. Our pipeline of molecular glues includes BTX-1188, a rationally designed, dual-targeting molecular glue degrader of GSPT1 and IKZF1/3 for acute myeloid leukemia and solid tumors, and undisclosed oncology targets through our research collaboration and license agreement with Incyte. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Investors/Media
Argot Partners
212.600.1902
[email protected]

 

Collaboration will leverage Biotheryx’s PRODEGY platform to discover molecular glue degraders for multiple historically undruggable novel oncology targets

Biotheryx to receive approximately $13 million from Incyte for the initial target, including an upfront technology access fee of $7 million plus potential R&D funding of $6 million

Biotheryx also eligible to receive up to $347 million in potential future regulatory and commercial milestones for the initial target

SAN DIEGO, CA., April 5, 2023 — Biotheryx, Inc., a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders with a focus on validated targets in cancer and inflammatory disease, today announced it has entered into a Research Collaboration and License agreement with Incyte to discover and develop targeted protein degraders for novel oncology targets.

“We are pleased to embark on this collaboration with Incyte to identify targeted protein degraders for novel oncology targets. Biotheryx and Incyte share a commitment to finding new, transformative treatment options for people living with cancer,” said Philippe Drouet, President and Chief Executive Officer of Biotheryx. “Our PRODEGY platform is designed to increase efficiency in degrader discovery and design, enabling the development of therapies for previously undruggable targets. We look forward to leveraging this differentiated approach in our collaboration with Incyte and in the continued advancement of our pipeline of first-in-class, next generation bifunctional degraders and molecular glues for the treatment of cancers and inflammatory disease.”

Under the terms of the agreement, Biotheryx will utilize its distinctive PRODEGY platform to identify and initially develop molecular glue degraders for multiple historically undruggable oncology targets. For the initial target, Biotheryx will receive a technology access fee of $7 million plus up to an additional $6 million in potential research and development funding from Incyte for costs associated with the collaboration. Biotheryx is also eligible to receive potential future regulatory and commercial milestones of up to $347 million plus tiered single-digit royalties on global net product sales for the initial target. Incyte will be solely responsible for further development and commercialization of any molecular glue degraders discovered by Biotheryx’s PRODEGY platform. Additionally, under the terms of the agreement, the collaboration can be expanded under the same financial terms. Further financial terms of the deal were not disclosed.

“As we work to transform the oncology treatment landscape, Incyte is harnessing breakthrough science that may offer patients with unmet needs new treatment options,” said Dashyant Dhanak, Ph.D., Executive Vice President and Chief Scientific Officer of Incyte. “The Biotheryx team has significant expertise in targeted protein degradation, one of the most promising modalities in oncology, and we look forward to collaborating to develop therapies that can help improve patient lives.”

About Biotheryx, Inc.

Biotheryx is a biopharmaceutical company discovering and developing a portfolio of first-in-class protein degraders, including bifunctional degraders and molecular glues. Our initial focus is on deploying the differentiated potential of degraders towards validated targets in cancer and inflammatory disease. Members of our founding and scientific teams previously developed the first U.S. Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation, and we have applied our expertise in Cereblon binding to build our proprietary PRODEGY platform. Our pipeline of bifunctional degraders includes the first-ever degraders of SOS1 for pan-KRAS mutant cancers, CDK4/6 for solid tumors and PDE4 for inflammatory diseases. Our pipeline of molecular glues includes BTX-1188, a rationally designed, dual-targeting molecular glue degrader of GSPT1 and IKZF1/3 for acute myeloid leukemia and solid tumors. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Biotheryx Investors/Media
Argot Partners
[email protected]

Incyte Investors/Media
Investors – Christine Chiou
[email protected]

Media – Catalina Loveman
[email protected]