Carrick Therapeutics Ltd.

BOSTON, Sept. 23, 2024 (GLOBE NEWSWIRE) -- Carrick Therapeutics Inc., an oncology-focused biopharmaceutical company discovering and developing highly differentiated therapies, today announced that the first patient has been dosed in the Phase 1 clinical trial evaluating CT7439, a novel cyclin dependent kinase 12/13 (CDK12/13) inhibitor / Cyclin-K glue-degrader. CDK12/13 is implicated in multiple cancer types, as they regulate transcription elongation, RNA splicing, as well as cleavage and polyadenylation. DNA damage response genes are particularly suppressed by loss of CDK12/13 activity. The clinical trial is enrolling patients with advanced solid tumors, including ovarian, breast and Ewing's Sarcoma. "Initiation of our CT7439 Phase 1 clinical trial marks the advancement of our second therapeutic into the clinic for aggressive and resistant forms of cancer,” said Tim Pearson, Chief Executive Officer of Carrick Therapeutics. “CT7439 is the first CDK12/13 inhibitor to enter clinical development, and we are encouraged by its potential as monotherapy or combination therapy across multiple tumor types.” The Phase 1 clinical trial is a modular design, beginning with a dose escalation for the initial administration of CT7439 to patients. The initial clinical evaluation will be focused on safety and pharmacokinetics, with an opportunity for early Proof of Principle using a blood based pharmacodynamic assay of the homologous recombination repair (HRR) pathway. Clinical trial details can also be found on www.clinicaltrials.gov under study ID: NCT06600789. For additional information on the clinical trial, please contact hello@carricktherapeutics.com. About CT7439CT7439 is an inhibitor of CDK12/13 as well as a 'glue degrader' of Cyclin-K, which is the obligate co-factor for CDK12/13, giving both first-in-class and best-in-class potential. This dual modality significantly increases the potency of the compound and leads to the inhibition of DNA repair at the transcriptional level. CDK12/13 regulates gene transcription through the activation of RNA Polymerase II. It has the potential to synergise with other agents targeting DDR such as the PARP inhibitors in multiple cancer types, including breast, ovarian and Ewing’s Sarcoma. About Carrick TherapeuticsCarrick Therapeutics is an oncology-focused biopharmaceutical company developing highly differentiated novel therapies that address significant unmet needs. The Company’s lead program, samuraciclib, is a novel oral first-in-class inhibitor of CDK7 currently in multiple Phase 2 clinical trials for metastatic HR+ breast cancer. The Company is collaborating with Roche, Menarini Group and Arvinas/Pfizer to evaluate novel combinations of samuraciclib with oral SERD endocrine therapies. Additionally, Carrick is developing CT7439, a novel CDK12/13 inhibitor / Cyclin-K glue-degrader, which is currently in a Phase 1 clinical trial. For more information about Carrick Therapeutics, please visit www.carricktherapeutics.com Carrick Contact Carrick TherapeuticsJenny Horsfield, Chief Business Officerjenny.horsfield@carricktherapeutics.com Investors and MediaLuke Heagle, Real Chemistrylheagle@realchemistry.com

Exscientia has backed the CDK7 candidate as the company “believes GTAEXS617 has the potential to overcome significant safety and efficacy limitations of existing approved treatments”. Image Credit: Explode / Shutterstock. Exscientia has taken full ownership of an oral cyclin-dependent kinase 7 (CDK7) inhibitor after buying out its development partner GT Apeiron Therapeutics’ shares of the programme. The UK-based company paid $20m upfront, half in cash and the rest in equity. Following the transaction, Exscientia will bear all existing development costs for the drug but will pay sales royalties to GT Apeiron. The CDK7 candidate GTAEXS617 is being investigated in a Phase I/II dose escalation ELUCIDATE trial (NCT05985655). The therapy is being evaluated as both, a monotherapy and in combination with standard of care therapies, in patients with advanced or metastatic solid tumours. Exscientia expects a trial readout in H2 this year. Following the trial readout, the company plans to investigate GTAEXS617 as a combination therapy in recurrent or advanced hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients. Exscientia has supported the CDK7 candidate as the company “believes GTAEXS617 has the potential to overcome significant safety and efficacy limitations of existing approved treatments”. Additionally, the company says the therapy can overcome common resistance pathways associated with CDK4/6 inhibitors such as Pfizer ’s Ibrance (palbocilib) , and Novartis and Astex’s Kisqali (ribociclib ). See Also: Conflict means millions of children are missing vaccinations, UN says Moderna and Mitsubishi Tanabe link on mRNA vaccines in Japan There are no approved CDK7 inhibitors, and most are in early development. Another company developing a CDK7 inhibitor therapy is Carrick Therapeutics. The company is studying the drug samuraciclib (CT7001) as a combination therapy for breast cancer. A Phase II trial (NCT05963997) is investigating samuraciclib in combination with Menarini Group’s oral selective oestrogen receptor degrader, Orserdu (elacestrant), in HR+/HER2- metastatic breast cancer patients. Carrick is also investigating samuraciclib and Arvinas and Pfizer’s vepdegestrant, an investigational oral PROteolysis Targeting Chimera (PROTAC) oestrogen receptor protein degrader. The Phase I/II trial (NCT06125522) is evaluating the therapy in oestrogen receptor-positive (ER+) /HER2- advanced or metastatic breast cancer.

Exscientia is aiming to publish monotherapy dose escalation date this year. Exscientia has taken full ownership of its oral CDK7 inhibitor candidate, buying out partner GT Apeiron for $20 million. The AI-enabled biotech plans to advance the molecule into a breast cancer combination trial. GT Healthcare, an investor in Exscientia, launched GT Apeiron in 2019 and immediately signed a deal to fund the discovery of cancer drugs with the AI specialist. Exscientia and GT Apeiron terminated the first deal in 2021 and entered into a joint operation and cost sharing arrangement for the development and commercialization of multiple programs. The partners began a phase 1/2 clinical trial of the lead candidate, the oral CDK7 inhibitor GTAEXS617, in July 2023. Now, Exscientia has bought out its partner. GT Apeiron last disclosed funding when it raised a $17.5 million series A round in March 2022.  Exscientia is paying $10 million in upfront cash and a further $10 million in upfront equity to take control of the program and ownership of all intellectual property. GT Apeiron will receive single-digit royalties if GTAEXS617 comes to market. Exscientia will take on all existing development costs but still expects its runway to extend well into 2027. The arrangement gives Exscientia full ownership of an asset it believes can address the limitations that have held CDK7 inhibitors back to date. Eli Lilly took a CDK7 inhibitor into human testing in 2019 but stopped the trial over a lack of efficacy. Syros Pharmaceuticals dropped one asset, SY-1365, and another, SY-5609, is on the backburner. Carrick Therapeutics has pushed its prospect, samuraciclib, into phase 2.  Exscientia discussed the positioning of GTAEXS617 on an earnings call in May, telling investors that, while it expects to see some level of monotherapy activity, combinations will be the focus for clinical use. Toxicity is the barrier to combinations, including with immunotherapies. Ben Taylor, Exscientia’s chief financial and strategy officer, discussed why GTAEXS617 may be free from problems that affect some rival molecules.  “It was specially designed to get around an issue that a number of the other competitive molecules have, which is being a transporter substrate. We think we've got a really nice advantage there and hopefully you'll be able to see that in the data,” Taylor said. “Because if we can get a nice safe profile, this is a mechanism that clearly should work, and there's a number of different combination opportunities for it.” Exscientia is aiming to publish monotherapy dose escalation data this year. If all goes to plan, the biotech will start a dose escalation study combining GTAEXS617 with a selective estrogen receptor degrader in breast cancer around the end of the year.