Scholar Rock Demonstrates that Highly Specific TGFβ1 Inhibition Combined with Anti-PD1 Drives Tumor Regression and Survival Benefit in Preclinical Models of Primary Resistance to Checkpoint Blockade Therapy

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CAMBRIDGE, Mass., Nov. 09, 2018 (GLOBE NEWSWIRE) -- Holding Corporation (NASDAQ:SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which play a fundamental role, today announced new preclinical data from its TGFβ1 cancer immunotherapy program. In syngeneic mouse models of primary resistance to checkpoint blockade therapy (CBT), combination treatment with a highly specific inhibitor of TGFβ1, SRTβ1-Ab3, and an anti-PD1 antibody resulted in tumor regression or tumor control as well as significant survival benefit. In addition, adult rats treated with SRTβ1-Ab3 with weekly doses up to 100mg/kg for 4 weeks showed an improved preclinical toxicity profile compared to pan-TGFβ inhibition. Detailed results are being presented at the Society for Immunotherapy of Cancer’s (SITC) 33 Annual Meeting in Washington DC. 

“We are proud to be presenting these exciting results that demonstrate a highly specific TGFβ1 inhibitor overcomes primary resistance to checkpoint blockade therapy while minimizing the toxicities associated with pan-TGFβ inhibition,” said Nagesh Mahanthappa, Ph.D., President and CEO of Scholar Rock. “Despite the clinical breakthroughs achieved by cancer immunotherapy, there remains significant unmet need with a majority of patients failing to respond to checkpoint inhibition. These preclinical results, using models that we believe better emulate human tumors resistant to CBT, could potentially provide a new avenue in the pursuit of novel therapies for patients with cancer.”

TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly those for which CBT is an approved treatment. Based on analyses of human tumors that are resistant to CBT, TGFβ1 is implicated as a key contributor to immune exclusion that leads to primary resistance observed in patients.  Scholar Rock evaluated SRTβ1-Ab3, a highly specific inhibitor of TGFβ1, in syngeneic mouse tumor models sharing key features that can be observed in resistant human tumors:  high expression of TGFβ1 over TGFβ2 and TGFβ3, active TGFβ signaling, immune exclusion, and minimal to no response to anti-PD1/PDL1 therapy.  In these preclinical studies, treatment with SRTβ1-Ab3 drove effector cell infiltration and expansion and rendered solid tumors vulnerable to PD1 blockade.

Highlights from the preclinical data being presented at SITC for the poster, titled “Defeating checkpoint resistance: Highly specific inhibition of latent TGFβ1 activation renders resistant solid tumors vulnerable to PD-1 blockade” (Poster #550), include:

* For MBT-2: Response provides percentage of animals that achieved a tumor volume at study end of less than 25% of the 1,200mm survival threshold.** For Cloudman S91: Response provides percentage of animals that achieved a tumor volume at the interim study cutoff of less than 25% of the 2,000mm survival threshold. This study is ongoing to continue assessment of response durability.

Scholar Rock will host an investor and analyst event beginning at 2:00 p.m. ET on Saturday, November 10, 2018. The live webcast may be accessed by visiting the Investors & Media section of the Scholar Rock website at .  An archived replay of the webcast will be available on the Company’s website for approximately 90 days following the presentation.

The poster can be accessed at: 

Scholar Rock Contact:
Catherine Hu

Media Contact:
The Yates Network
Kathryn Morris


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Globe Newswire: 13:00 GMT Friday 9th November 2018

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