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Replies to post #210703 on Biotech Values
04/24/17 12:42 PM
Overview
We are a clinical-stage biopharmaceutical company focused on the discovery and development of novel therapeutics for the treatment of cancer. Our two clinical assets are based on our core understanding of cyclin-dependent kinases, or CDKs, a family of proteins that play an important role in the growth and proliferation of all human cells. Two particular CDKs, CDK4 and CDK6, collectively known as CDK4/6, represent a validated and promising class of targets for anti-cancer therapeutics. We have leveraged our deep expertise in CDK4/6 biology to discover and develop two highly potent and selective CDK4/6 inhibitors that may have broad applicability across multiple cancer indications. We believe we are the only company with two distinct clinical-stage CDK4/6 inhibitors, trilaciclib and G1T38, each of which has the potential to be the backbone therapy of multiple combination regimens.
CDK4/6 is required for growth and proliferation in certain normal cell types, such as hematopoietic stem and progenitor cells, or HSPCs. HSPCs reside in the bone marrow and are the “reservoir” from which all blood and immune system cells are formed. Additionally, CDK4/6 plays an integral role in the growth and proliferation of certain types of tumors. Tumors that rely on CDK4/6 to grow and proliferate are referred to as CDK4/6-dependent tumors, and include the most common kinds of prostate and breast cancer. Alternatively, some tumors can grow and proliferate without CDK4/6 activity and are referred to as CDK4/6-independent. CDK4/6 independent tumors include small cell lung cancer, or SCLC, and triple-negative breast cancer, or TNBC. Our two CDK4/6 inhibitors were rationally designed to treat distinct patient populations with different combination regimens. Trilaciclib is in development in combination with chemotherapy for the treatment of patients with CDK4/6-independent tumors. G1T38 is in development in combination with targeted therapies for the treatment of patients with CDK4/6-dependent tumors.
Product candidates
Trilaciclib, our most advanced candidate, is a potential first-in-class intravenous CDK4/6 inhibitor we rationally designed to preserve HSPCs and enhance immune system function during chemotherapy. Chemotherapy has significant clinical utility and continues to be the most effective treatment for many cancers. However, it also damages HSPCs (myelosuppression) and the immune system (immunosuppression), leading to severe adverse effects and limiting anti-tumor activity. We believe that if the beneficial effects of chemotherapy (i.e. potent tumor cell killing) could be maximized, while minimizing the deleterious side-effects of myelosuppression and immunosuppression, patient outcomes would be significantly improved.
In the open-label Phase 1b parts of two Phase 1b/2a trials of trilaciclib and chemotherapy in SCLC, response rates and tolerability have compared favorably to historical chemotherapy-only trials. For example, in 17 evaluable patients in the Phase 1b part of the trial in first-line SCLC patients, we have seen an 88% response rate (including one complete response, or CR) and a clinical benefit rate of 94%. In historical chemotherapy-only trials, the response rates are approximately 50% and the CR rates are less than 1%. In the Phase 1b parts of these two trials, we have treated 51 patients with over 250 cycles of trilaciclib and chemotherapy, and have not had a single episode of febrile neutropenia – one of the most common adverse consequences of these chemotherapy regimens. Based on these compelling results, we initiated the randomized, placebo-controlled Phase 2a parts of these SCLC trials, as well as a randomized Phase 2 trial in patients with TNBC. Initial data from these trials are expected to be released in 2018.
To our knowledge, we are the only company developing a CDK4/6 inhibitor specifically for use with chemotherapy. We believe that trilaciclib has the potential to transform the chemotherapy treatment paradigm and significantly benefit patient outcomes. Additionally, based upon robust preclinical data, we believe that trilaciclib has the potential to significantly enhance the efficacy of checkpoint inhibitor/chemotherapy combinations. In December 2016, we entered into a non-exclusive collaboration with Genentech to evaluate trilaciclib in combination with Genentech’s checkpoint inhibitor Tecentriq to realize this potential.
G1T38, our second clinical-stage candidate, is a potential best-in-class oral CDK4/6 inhibitor being developed to be used in combination with other targeted therapies to treat multiple cancers. We rationally designed G1T38 to improve upon and address the shortcomings of the approved CDK4/6 inhibitors Ibrance and Kisqali and others in development. Our preclinical data and early clinical data indicate the potential for continuous daily dosing and improved antitumor activity and tolerability. A Phase 1 trial of G1T38 in 75 healthy volunteers showed a favorable safety profile leading to the initiation of a Phase 1/2 trial in ER+, HER2- breast cancer (in combination with Faslodex) in January 2017. Preliminary results from the first six patients enrolled in the Phase 1/2 trial suggest that G1T38 may be able to address the shortcomings of the other CDK4/6 inhibitors. Our plans for G1T38 include combinations in other cancers, such as non-small cell lung cancer, or NSCLC, where we expect to begin a Phase 2 trial in 2018 in combination with an EGFR inhibitor. We believe that G1T38 has the potential to be the backbone therapy of multiple proprietary combination regimens.
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