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CAMBRIDGE, Mass., April 02, 2019 (GLOBE NEWSWIRE) -- Scholar Rock Holding Corporation (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, today announced additional data that further elucidate the mechanism of action of a highly specific inhibitor of TGFβ1 activation in syngeneic mouse tumor models that emulate clinically-observed primary resistance to checkpoint blockade therapy (CBT). Detailed preclinical results are being presented at the American Association for Cancer Research (AACR) annual meeting in Atlanta, GA on April 2, 2019.
The preclinical data demonstrate that treatment with SRK-181-mIgG1, a highly specific inhibitor of TGFβ1 activation, in combination with an anti-PD1 immunotherapy, can drive tumor regression or control, resulting in significant survival benefit compared to anti-PD1 monotherapy. This was shown across multiple tumor models, including the EMT6 breast cancer mouse model, which expresses both TGFβ1 and TGFβ3 isoforms. In addition, newly presented immune response data show that combination treatment leads to infiltration and expansion of CD8+ T cells and a reduction of immunosuppressive myeloid cells, suggesting TGFβ1's multiple contributions to primary resistance to CBT.
“These new preclinical results reinforce our belief that a highly specific inhibitor of TGFβ1 activation can enable the immune response to overcome a key mechanism of primary resistance to checkpoint blockade therapy, even in tumors that express other TGFβ isoforms, and could meaningfully expand the number of patients who could benefit from checkpoint blockade therapies,” said Nagesh Mahanthappa, Ph.D., President and CEO of Scholar Rock. “With the recently announced nomination of SRK-181 as the first product candidate in our cancer immunotherapy program, we are eagerly working towards initiating a Phase 1 trial in patients with solid tumors in mid-2020.”
Highlights from the preclinical data being presented at AACR for the poster titled “Defeating primary checkpoint resistance: SRK-181 is a first-in-class, fully human antibody that renders resistant tumors sensitive to anti-PD-1” (Poster #4090), include:
(Response*: %, N)
(Response**: %, N)
(Response***: %, N)
|Control||0% (0/9)||0% (0/13)||0% (0/11)|
|Anti-PD1 monotherapy||0% (0/9)||0% (0/13)||17% (2/12)|
|SRK-181-mIgG1 monotherapy||0% (0/10)||0% (0/12)||0% (0/12)|
|Anti-PD1/SRK-181-mIgG1, 3 mg/kg||NT||29% (4/14)||83% (10/12)|
|Anti-PD1/SRK-181-mIgG1, 10 mg/kg||50% (5/10)||57% (8/14)||78% (7/9)|
|Anti-PD1/SRK-181-mIgG1, 30 mg/kg||NT||NT||73% (8/11)|
* For EMT6: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 2,000mm3 survival threshold.
** For MBT-2: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 1,200mm3 survival threshold.
*** For Cloudman S91: Response is defined as animals that achieved a tumor volume at study end of less than 25% of the 2,000mm3 survival threshold.
NT: Not tested
The poster can be accessed at: https://scholarrock.com/platform/publications/
SRK-181 is a highly specific inhibitor of TGFβ1 activation being developed to overcome primary resistance to checkpoint blockade therapies (CBTs). TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on analyses of human tumors that are resistant to CBT, TGFβ1 is implicated as a key contributor to exclude immune cell entry into the tumor microenvironment, thereby preventing normal immune function. By overcoming this immune cell exclusion, SRK-181 has the potential to induce tumor regression when administered in conjunction with CBT.
About Scholar Rock
Scholar Rock is a clinical-stage biopharmaceutical company focused on the discovery and development of innovative medicines for the treatment of serious diseases in which signaling by protein growth factors plays a fundamental role. Scholar Rock is creating a pipeline of novel product candidates with the potential to transform the lives of patients suffering from a wide range of serious diseases, including neuromuscular disorders, cancer, fibrosis and anemia. Scholar Rock’s newly elucidated understanding of the molecular mechanisms of growth factor activation enabled it to develop a proprietary platform for the discovery and development of monoclonal antibodies that locally and selectively target these signaling proteins at the cellular level. By developing product candidates that act in the disease microenvironment, the Company intends to avoid the historical challenges associated with inhibiting growth factors for therapeutic effect. Scholar Rock believes its focus on biologically validated growth factors may facilitate a more efficient development path. For more information, please visit www.ScholarRock.com or follow Scholar Rock on Twitter (@ScholarRock) and LinkedIn.
Scholar Rock® is a registered trademark of Scholar Rock, Inc.
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding the ability of SRK-181 to render tumors vulnerable to checkpoint blockade therapy, including the inhibitor’s ability to affect tumor regression, tumor control or survival; the toxicity profile of SRK-181 ; and the timeline for and progress in developing SRK-181. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward-looking statements. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include the reproducibility of any preclinical data presented; preclinical data and testing of SRK-181 may not be predictive of the results or success of clinical trials; the development of SRK-181 will take longer and/or cost more than planned; SRK-181 will not receive regulatory approval; any data generated from Scholar Rock’s future nonclinical studies and clinical trials; and those risks more fully discussed in the section entitled "Risk Factors" in Scholar Rock’s Annual Report on Form 10-K for the quarter and full year ended December 31, 2018, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock’s subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent Scholar Rock’s views only as of today and should not be relied upon as representing its views as of any subsequent date. All information in this press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law.
Scholar Rock Contact: Investors/Media Catherine Hu email@example.com 917-601-1649 Media Contact: The Yates Network Kathryn Morris firstname.lastname@example.org 914-204-6412