Author: biotheryx

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]

SAN DIEGO, CA. February 15, 2023 — Biotheryx, Inc., a clinical stage company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, today announced that members of its senior management team will participate in two panel discussions at the Wells Fargo 2023 Targeted Protein Degradation Virtual Summit, being held virtually on Tuesday, February 21, 2023. Details for the panel discussions are as follows:

Panel Discussion: Overcoming Resistance with Targeted Protein Degradation
Speaker: Aparajita Hoskote Chourasia, M.S., Ph.D., Vice President, Biology
Date and Time: Tuesday, February 21, 2023, at 8:00 a.m. EST
Webcast link: Available here

Panel Discussion: Degradation vs. Inhibition – When does Targeted Protein Degradation Make Sense and When Does It Not?
Speaker: Leah Fung, Ph.D., Chief Scientific Officer
Date and Time: Tuesday, February 21, 2023, at 1:00 p.m. EST
Webcast link: Available here

A replay of the webcasts will be archived for up to 6 months following the event.

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. 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 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.  Our pipeline of bifunctional degraders includes the first-ever degraders of SOS1 for pan-KRAS mutant cancers, CDK4/6 and CDK2/4/6 for solid tumors and PDE4 for inflammatory diseases. 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 from degrader program targeting SOS1 for KRAS mutant cancers to be presented in keynote plenary session

Latest preclinical data for BTX-1188, a degrader of GSPT1 and IKZF1/3, to be presented

SAN DIEGO, CA. October 24, 2022 — Biotheryx, Inc., a clinical stage company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, today announced that it will present preclinical data from its targeted protein degrader programs at the 5^th Annual Targeted Protein Degradation Summit, being held October 25-28, 2022, in Boston, Massachusetts.

Leah Fung, Ph.D., Chief Scientific Officer of Biotheryx, will present as a Keynote Plenary Speaker in a session, “Highlighting Key Discoveries of Bifunctional Degraders to New Targets,” to highlight novel small molecule bifunctional degraders of son of sevenless homolog 1 (SOS1), potent inhibitors of Kirsten rat sarcoma (KRAS) mutant cancers. Aparajita Chourasia, Ph.D., Vice President of Biology of Biotheryx will also present the latest preclinical data in support of the Company’s BTX-1188 molecular glue program targeting GSPT1 and IKZF1/3.

“We are looking forward to sharing findings at the TPD Summit that highlight the potential of our innovative PRODEGY platform to develop new and exciting cancer therapies,” said Dr. Fung. “The data Biotheryx are presenting are evidence of our team’s commitment to the discovery and design of first-in-class protein degraders.”

Details for Biotheryx’s presentations at the 5^th Annual TPD Summit are as follows:

Keynote Plenary Session: Highlighting Key Discoveries of Bifunctional Degraders to New Targets
Presentation: Novel Small Molecule Bifunctional Degraders of SOS1 For Inhibition of Pan-KRAS Mutant Cancers
Presenter: Leah Fung, Ph.D., CSO
Date and Time: Thursday, October 27, 2022, at 8:30 a.m. EST 

Presentation: BTX-1188, a First-in-Class Dual Degrader of GSPT1 and IKZF1/3, for Treatment of Acute Myeloid Leukemia (AML) and Solid Tumors
Presenter: Aparajita Hoskote Chourasia, Ph.D.
Session: Late Breaking Update of Clinical Monovalent Degraders
Date and Time: Wednesday, October 26, 2022, at 2:30 p.m. EST

About Biotheryx, Inc.

Biotheryx is a clinical stage biopharmaceutical company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, with an initial focus on cancer and inflammatory disorders. 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 have applied their expertise in Cereblon binding to build our proprietary PRODEGY platform. Our lead product candidate, BTX-1188, is a rationally designed dual-targeting molecular glue degrader of GSPT1 and IKZF1/3, which we are currently developing in a Phase 1/2 clinical trial in acute myeloid leukemia and solid tumor patients. Our pipeline of first-in-class degrader programs includes degraders of SOS1 for KRAS mutant cancers, CDK2/4/6 for solid tumors and PDE4 for auto-immune and inflammatory diseases. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Investors/Media
Argot Partners
212.600.1902
[email protected]

Ms. Lawhon has nearly 20 years of oncology drug development, partner engagement and corporate strategy leadership experience

SAN DIEGO, CA. August 24, 2022 — Biotheryx, Inc., a clinical stage company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, today announced the appointment of Tracy Lawhon, J.D., as Chief Development Officer (CDO).

“We are thrilled to welcome Tracy to Biotheryx as our Chief Development Officer,” said Philippe Drouet, President and Chief Executive Officer (CEO) of Biotheryx. “She brings a tremendous depth of expertise, having led drug development and other strategic initiatives at clinical and commercial stage biopharmaceutical companies, and she shares our commitment to advancing new medicines for people with cancer and other diseases. I am confident that Tracy’s entrepreneurial approach and knowledge will enhance our development strategy and capabilities as we progress our pipeline of TPDs.”

“I am honored to join the protein degradation pioneers at Biotheryx and help build it into a leading next-generation TPD company to better support patients with cancers and other serious diseases,” said Ms. Lawhon. “The Company’s pipeline and proprietary PRODEGY platform show great potential, and I am excited to collaborate with the talented Biotheryx team to bring innovative new therapies to patients.”

Ms. Lawhon previously served as Vice President of Strategic Development and Clinical Operations at Valo Health Inc., where she co-led clinical development and led pharmaceutical sciences using real world data and modeling to advance two cardiovascular/metabolism assets into Phase 2 development and led pharmaceutical sciences through acquisition and IND-enabling development of a biologic for oncology. Prior, Ms. Lawhon  was a founding executive at Adastra Pharmaceuticals, Inc. (formerly Tragara), where she held roles including Chief Operating Officer, Interim CEO and CDO. During her tenure, she drove the strategic and operational development of drug candidates and designed and executed regulatory strategies and submissions for multiple IND applications. Ms. Lawhon also held leadership roles at Cabrellis Pharmaceuticals, Novartis and Schering-Plough Research Institute. She earned her J.D. from Indiana University School of Law and B.S. in Microbiology from Indiana University.

About Biotheryx, Inc.

Biotheryx is a clinical stage biopharmaceutical company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, with an initial focus on cancer. Members of our founding and scientific teams previously developed the first Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation, and have applied their expertise in Cereblon binding to build our proprietary PRODEGY platform. Our lead product candidate, BTX-1188, is a rationally designed dual-targeting molecular glue degrader of GSPT1 and IKZF1/3, which we are currently developing in a Phase 1/2 clinical trial in acute myeloid leukemia and solid tumor patients. Our broad and growing pipeline includes degraders of SOS1 for KRAS mutant cancers and CDK2/4/6 for solid tumors, with a goal of submitting three additional investigational new drug (IND) applications to the FDA over the next three years. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Investors/Media
Argot Partners
212.600.1902
[email protected]

BTX-1188 Showed Deep and Durable Dual Degradation of GSPT1 and IKZF1/3 In Vitro Along with Beneficial Immunomodulatory Properties

Data Support Ongoing Phase 1 Development for the Treatment of Hematologic and Solid Tumor Malignancies

SAN DIEGO, CA. May 26, 2022 — Biotheryx, Inc., a clinical stage company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, today announced that its abstract highlighting supportive preclinical data for its lead asset BTX-1188, a potentially first-in-class, dual protein degrader of GSPT1 and IKZF1/3, will be presented in a poster at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 3-7, 2022, in Chicago, Illinois and virtually.

“Our distinctive PRODEGY platform is designed to enable the discovery and development of a broad range of targeted protein degrader molecules and BTX-1188 is the first of our pipeline to enter the clinic,” said Leah Fung, Ph.D., Chief Scientific Officer of Biotheryx. “BTX-1188 is a molecular glue that was rationally designed to degrade  GSPT1 and IKZF1/3. The data being presented at ASCO 2022 support the ongoing Phase 1 clinical trial evaluating BTX-1188 in patients with hematologic and solid tumor cancers and demonstrate what we believe to be our ability to design first-in-class molecular glues with the potential to improve clinical outcomes for patients with cancer and other serious diseases.”

“We are leveraging our deep expertise with the modulation of Cereblon, the only clinically and commercially validated E3 ligase, to design innovative targeted protein degraders with the potential to address significant unmet medical need,” said Philippe Drouet, President and Chief Executive Officer of Biotheryx. “We look forward to presenting these pre-clinical data from our lead program, BTX-1188, at ASCO 2022.”

Key Highlights from BTX-1188 Preclinical Results

• BTX-1188 has shown deep and durable degradation of GSPT1 and IKZF1/3 and inhibition of MYC in several types of hematologic and solid tumor cell lines, including lymphoma, diffuse large B-cell lymphoma, non-small cell lung cancer and glioma.
• BTX-1188 has shown inhibition of pro-inflammatory cytokines and enhancement of immune stimulatory cytokines, owing to IKZF1/3 degradation, which may prevent the known systemic inflammatory dose-limiting toxicities associated with pure GSPT1 degradation (Uy 2019)¹.
• BTX-1188 potently inhibits tumor cell proliferation and tumor growth in ex vivo and in vivo models of acute myeloid leukemia (AML) and in in vitro and in vivo models of lung, breast and ovarian cancer.
• These preclinical results support the ongoing Phase 1 clinical evaluation of BTX-1188 in patients with AML and certain solid tumors, especially in MYC-dependent cancers.

Details for the BTX-1188 ASCO 2022 poster presentation are as follows:

Title: BTX-1188, a first-in-class dual degrader of GSPT1 and IKZF1/3, for treatment of acute myeloid leukemia (AML) and solid tumors
Presenter: Aparajita Hoskote Chourasia, Ph.D.
Abstract Number: 7025
Poster Number: 256
Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
Date and Time: Saturday, June 4, 2022 at 9:00 a.m. CT (10:00 a.m. ET)

This poster presentation will be available on the ASCO Meeting website.  Following the presentation at the meeting, a PDF copy of the poster will be available in the “Publications and Presentations” section of Biotheryx’s website.

About BTX-1188

Biotheryx’s lead molecular glue drug candidate BTX-1188 is a dual protein degrader which was designed to degrade GSPT1, a promising cancer target, and IKZF1/3 (also known as Ikaros/Aiolos), both clinically validated anti-inflammatory and immunomodulatory targets. Prior literature has demonstrated that degradation of GSPT1 can result in antitumor activity in difficult-to-treat tumors such as acute myeloid leukemia (AML) and in solid tumors, including those that overexpress oncogenic transcription factors, such as MYC, however, prior clinical research by others has shown that administration of a GSPT1-only degrader was associated with dose-limiting toxicities related to the release of pro-inflammatory cytokines. BTX-1188 was specifically designed as a potent degrader of GSPT1 that can also directly block inflammation by degrading IKZF1/3. In preclinical studies conducted by Biotheryx, administration of BTX-1188 led to complete eradication of tumors and extended survival in xenograft models of AML. BTX-1188 also led to potent cell killing in a number of cell lines derived from solid tumors. BTX-1188 is currently being evaluated in a Phase 1 dose-escalation trial in patients with hematologic and solid tumor malignancies.

About Biotheryx, Inc.

Biotheryx is a clinical stage biopharmaceutical company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, with an initial focus on cancer. 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 have applied their expertise in Cereblon binding to build our proprietary PRODEGY platform. Our lead product candidate, BTX-1188, is a rationally designed dual-targeting molecular glue degrader of GSPT1 and IKZF1/3, which we are currently developing in a Phase 1/2 clinical trial in acute myeloid leukemia and solid tumor patients. Our broad and growing pipeline includes degraders of SOS1 for KRAS mutant cancers and CDK2/4/6 for solid tumors, with a goal of submitting three additional investigational new drug (IND) applications to the FDA over the next three years. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.

Contacts:

Investors/Media
Argot Partners
212.600.1902
[email protected]

¹ Uy, G.L., et al. Blood 134 (Supplement_1): 232 (2019)

Mr. Caravella has more than 20 years of healthcare finance experience, including at Tango Therapeutics and Johnson & Johnson

SAN DIEGO, April 25, 2022 /PRNewswire/ — Biotheryx, Inc., a clinical stage company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, today announced the appointment of Jeff Caravella as Chief Financial Officer.

“Throughout Jeff’s healthcare industry tenure, he has led finance organizations impacting corporate, business development, commercial and operational strategies that supported these companies’ greater missions to create innovative healthcare solutions and medicines for patients,” said Philippe Drouet, President and Chief Executive Officer of Biotheryx. “We are glad to welcome Jeff to our leadership team as we advance the clinical development of our lead protein degrader product candidate BTX-1188 and the rest of our product candidate pipeline to create better medicines for patients.”

“I’m honored to join Biotheryx at an important time for the Company and the protein degradation field. I look forward to playing a key role in Biotheryx’s future in leveraging PRODEGY, the Company’s proprietary platform for the discovery and development of potentially first-in-class TPDs,” said Mr. Caravella. “I look forward to partnering with this team to execute on its strategy and help realize the potential of their platform, innovative product candidate pipeline and commitment to finding solutions for patients.”

Mr. Caravella previously served as Vice President of Finance at Tango Therapeutics, a public biotechnology company where he built and led the finance and accounting organization. Prior, he held finance roles across commercial, business development and operations functions at other publicly-held companies, including Editas Medicine, Charles River Laboratories and Johnson & Johnson. During his 10-year tenure at Johnson & Johnson, he spent two years as the Head of Finance for the Johnson & Johnson Boston Innovation Center, where he led the assessment and strategy for multiple business development and licensing deals. Mr. Caravella earned his M.B.A. and B.S. from Syracuse University.

About Biotheryx, Inc.

Biotheryx is a clinical stage biopharmaceutical company discovering and developing a portfolio of innovative small molecule targeted protein degraders (TPDs) in areas of high unmet medical need, with an initial focus on cancer. Members of our founding and scientific teams previously developed the first Food and Drug Administration (FDA) approved modulators of Cereblon, the most widely validated E3 ligase involved in protein degradation, and have applied their expertise in Cereblon binding to build our proprietary PRODEGY platform. Our lead product candidate, BTX-1188, is a rationally designed dual-targeting molecular glue degrader of GSPT1 and IKZF1/3, which we are currently developing in a Phase 1/2 clinical trial in acute myeloid leukemia and solid tumor patients. Our broad and growing pipeline includes degraders of SOS1 for KRAS mutant cancers and CDK2/4/6 for solid tumors, with a goal of submitting three additional investigational new drug (IND) applications to the FDA over the next three years. For more information, please visit www.biotheryx.com and engage with us on LinkedIn.