On April 21, 2021 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease through the inhibition of SEMA4D, reported the publication of results from the company’s CLASSICAL-Lung clinical trial in the journal Clinical Cancer Research, a publication of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Vaccinex, APR 21, 2021, View Source [SID1234578306]). CLASSICAL-Lung was a Phase 1b/2 trial evaluating the company’s lead clinical candidate, pepinemab, in combination with the immune checkpoint inhibitor BAVENCIO (avelumab) for the treatment of non-small cell lung cancer (NSCLC).

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The paper, entitled, "A Phase 1b/2 Study of Pepinemab in Combination with Avelumab in Advanced Non-Small Cell Lung Cancer," presents data showing that pepinemab is clinically active when combined with BAVENCIO and was well tolerated, with no identified safety concerns. The combination appeared to halt or reverse tumor progression (partial response or stable disease) in a subset of both immunotherapy naïve patients, including patients with often difficult to treat PD-L1–negative or PD-L1–low tumors, and some patients with primary or acquired resistance to prior single-agent anti-PD-1/L1 therapy.

Among 21 evaluable immunotherapy naïve patients, most of whom had negative or low tumoral expression of the PD-L1 biomarker, five patients experienced partial responses, four patients evidenced clinical benefit at or greater than one year, and the disease control rate (DCR) was 81%. Notably, the objective response rate (ORR) with the combination therapy was higher than previously reported for single agent avelumab in the PD-L1 negative / low population. Among 29 evaluable patients who previously experienced disease progression during or following anti-PD-1/L1 immunotherapy, the subsequent combination treatment resulted in a DCR of 59%, including two partial responses and seven patients with durable clinical benefit of at least 23 weeks. Finally, exploratory biomarker analysis from biopsies demonstrated improved penetration of killer CD8+ T cells into the tumor.

Dr. Maurice Zauderer, President and CEO of Vaccinex, stated, "The results of the CLASSICAL-Lung study support our hypothesis that adding pepinemab to a checkpoint inhibitor for the treatment of NSCLC can shift the tumor microenvironment toward anti-tumor immunity and away from immunosuppression. This appears to enhance the efficacy of checkpoint inhibition, even in some patients who did not respond to prior anti-PD-1/L1 therapies. We are very pleased to have the full data set published in this prestigious peer-reviewed medical journal and look forward to the continued development of this promising combination for the treatment of NSCLC. We are particularly pleased to shortly begin a new study of the combination of pepinemab and Keytruda (pembrolizumab) in front-line Head & Neck cancer."

The publication is now available electronically at: View Source

About the CLASSICAL – Lung Clinical Trial

The design of the trial consisted of a 12-subject dose escalation phase to determine the recommended Phase 2 dose of pepinemab in combination with avelumab, followed by a 50-subject dose expansion phase. The study included a total of 21 evaluable patients who were immunotherapy naïve and 32 patients who were refractory or resistant to prior treatment with immune checkpoint inhibitors (predominantly anti–PD-1). The primary objective was to assess safety and tolerability. Secondary objectives included evaluation of efficacy, immunogenicity, and PK/PD. An exploratory objective was to identify candidate biomarkers of activity.

On April 21, 2021 PerkinElmer, Inc. (NYSE: PKI), a global leader committed to innovating for a healthier world, reported that the Company will present at the BofA Securities 2021 Virtual Health Care Conference on Wednesday, May 12, 2021 at 9:30 a.m. ET (Press release, PerkinElmer, APR 21, 2021, View Source [SID1234578305]).

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Prahlad Singh, president and chief executive officer of PerkinElmer, will provide an update on the Company and its strategic priorities.

A live audio webcast of the presentation will also be available on the Investors section of the Company’s website at www.perkinelmer.com. A replay of the presentation will be posted on the PerkinElmer website after the event and will be available for 90 days following.

On April 21, 2021 RNAimmune, Inc., a biopharmaceutical company specializing in discovery and development of mRNA-based therapeutics and vaccines, reported execution of definitive agreements for a seed round financing of $10 million (Press release, Sirnaomics, APR 21, 2021, View Source [SID1234578304]). RNAimmune is a spin-off entity from Sirnaomics, a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases. Smooth River and Hong Kong Hongrun led the investment, with participation from Shanghai Walga Biotechnology, High Forest Investment and Terra Magnum Sigma. Sirnaomics also increased its investment in RNAimmune. This financing will allow RNAimmune to accelerate its research and development into mRNA vaccine and drug discovery focused on infectious disease, cancer, and rare diseases.

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Since its founding in early 2020, RNAimmune has built up its mRNA vaccine and drug discovery and development platform to tackle high unmet medical needs in infectious diseases, cancer and rare diseases. The Company is now in the IND enabling stage for its lead candidate COVID-19 mRNA vaccine and plans to file an IND with the U.S. Food and Drug Administration before the end of 2021. It is also advancing its RAS tumor vaccine program in collaboration with the University of California, Los Angeles. Headquartered in Maryland, United States, RNAimmune has set up its China R&D center in Guangzhou Bio-Island. Last August, the Company completed a seed financing round of $2.35 million.

"We are very pleased to see the exponential growth of RNAimmune, with completion of two rounds of financing in such a short time," said Patrick Lu, PhD, Chairman of the Board of RNAimmune. "The recent success of Moderna’s and BioNTech’s mRNA vaccines has demonstrated that mRNA technologies for development of novel therapeutics and vaccines are dramatically changing the landscape of the global pharmaceutical industry. RNAimmune has tremendous opportunities as a global mRNA innovating company."

On April 21, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported the initiation of patient enrollment into the ULTRA-V Phase 3 randomized trial, evaluating the time-limited triple combination of UKONIQ (umbralisib), the Company’s once-daily, inhibitor of PI3K-delta and CK1-epsilon, ublituximab, the Company’s investigational glycoengineered anti-CD20 monoclonal antibody, and venetoclax, compared to the continuous doublet combination of UKONIQ plus ublituximab (U2) in patients with both frontline and relapsed or refractory chronic lymphocytic leukemia (CLL) (Press release, TG Therapeutics, APR 21, 2021, View Source [SID1234578302]). The primary endpoint for the ULTRA-V Phase 3 trial is Progression-free Survival (PFS), and the trial is designed support the full approval of the triple combination of U2 plus venetoclax.

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The Company also announced completion of enrollment into the ULTRA-V Phase 2 global, single arm trial evaluating the triple combination of U2 plus venetoclax. This primary endpoint for this trial is overall response rate (ORR) and complete response (CR) rate, and the trial completed enrollment with approximately 165 patients enrolled. The trial enrolled patients with front line CLL, as well as relapsed or refractory CLL, including patients who were refractory to prior Bruton’s Kinase Inhibitor (BTK) therapy.

Richard R. Furman, MD, Director of CLL Research Center at Weill Cornell Medicine and Study Chair for the ULTRA-V Phase 2 and Phase 3 trials stated, "We are excited to launch this pivotal Phase 3 study based on the promising Phase 1 clinical results reported to date on the triplet combination of UKONIQ, ublituximab and venetoclax in patients with CLL. While recent approvals provide excellent treatment options for patients, disease progression and treatment tolerability still remain problematic for many patients. Our belief is that time-limited treatment regimens, such as U2 plus venetoclax, have the potential to produce meaningful responses without the need to expose patients to continuous therapy and related toxicities. We look forward to presenting the results of the Phase 2 portion of this study at a future medical meeting. I want to thank my colleagues for their strong support of the Phase 2 ULTRA-V trial and look forward to continuing and expanding our efforts now in Phase 3."

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "We are extremely pleased with the rapid enrollment seen in the ULTRA-V Phase 2 trial, with approximately 165 patients enrolled in approximately 16 months throughout a limited number of U.S. trial sites, with the majority of the enrollment taking place in 2020 during the height of the COVID-19 pandemic. We are further encouraged by the strong interest of new trial sites to participate in the Phase 3 portion of the trial. We believe the encouraging early results observed in the Phase 1 trial of U2 plus venetoclax, led by Dr. Paul Barr at the University of Rochester, which were most recently presented at the ASH (Free ASH Whitepaper) annual meeting in 2020, are supportive of our decision to quickly initiate the ULTRA-V Phase 2 and 3 trials. We look forward to providing an update from the Phase 1 trial later this year and initial results from the Phase 2 portion of the ULTRA-V trial in 2022."

ABOUT ULTRA-V PHASE 3 TRIAL
The ULTRA-V Phase 3 trial is an open-label, multicenter, randomized controlled clinical trial comparing the time-limited triple combination of UKONIQ and ublituximab (U2) plus venetoclax, to an active control arm of continuous U2. The Phase 3 trial includes two independent randomized cohorts of CLL subjects: a treatment-naïve cohort and a previously treated cohort, with each cohort being enrolled and evaluated independently of each other. The primary endpoint for the trial is Progression-free Survival (PFS). This trial is being led by Richard R. Furman, MD, Director of CLL Research Center at Weill Cornell Medicine and targeting over 60 U.S. trial sites.

ABOUT ULTRA-V PHASE 2 TRIAL
The ULTRA-V Phase 2 trial, (NCT03801525), is an open-label, multicenter, trial designed to investigate the efficacy and safety of ublituximab and UKONIQ combined with venetoclax in subjects with CLL. The primary endpoint of the trial is overall response rate (ORR) and Complete Response (CR) rate. The trial enrolled approximately 165 patients with front line and previously treated CLL at 26 sites throughout the United States.

ABOUT U2 PLUS VENETOCLAX PHASE 1 TRIAL
The Phase 1/2 trial, (NCT03379051), is a multi-center, dose-escalation trial designed to assess the safety and efficacy of U2 plus venetoclax in patients with relapsed or refractory CLL. The primary objective of the trial is to evaluate the safety of venetoclax after U2 induction. The secondary objectives are clinical efficacy as defined by ORR (including CR rate), PFS, and undetectable minimal residual disease (MRD) rate after 12 cycles of therapy. The trial enrolled approximately 50 CLL patients, and interim results were most recently presented on 43 CLL patients at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December 2020.

ABOUT CHRONIC LYMPHOCYTIC LEUKEMIA
Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia. It is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States in 2020 and approximately 45,000 new cases globally in 2020.1,2 Although signs and symptoms of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of malignant cells.

On April 21, 2021 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage precision oncology company focused on developing targeted therapies to inhibit frontier targets in RAS-addicted cancers, reported dosing of the first patient in a multicenter Phase 1/1b clinical trial evaluating RMC-5552, the company’s investigational first-in-class bi-steric mTORC1 inhibitor as a monotherapy (Press release, Revolution Medicines, APR 21, 2021, View Source [SID1234578301]). The trial is an open-label dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, preliminary efficacy and pharmacokinetics of RMC-5552 in patients with advanced relapsed/refractory solid tumors. Results from this study will inform Revolution Medicines’ identification of the maximum tolerated dose (MTD) and selection of recommended Phase 2 dose and schedule (RP2DS) for further evaluation of the compound.

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RMC-5552 is a potent and selective inhibitor of mTORC1 that is being developed as an anticancer therapeutic for patients with solid tumors that have hyperactivation of the mTOR pathway, including certain RAS-addicted cancers. The compound is designed to inhibit mTORC1 and preserve the natural tumor suppressive activity of 4EBP1, without the undesired inhibition of mTORC2. RMC-5552 has demonstrated antitumor activity in a wide variety of preclinical models. Revolution Medicines has also reported in vivo data demonstrating that RMC-5552 may increase antitumor activity in combination with KRASG12C inhibitors in lung and colon cancers harboring KRAS mutations and co-mutations in the mTOR signaling pathway that can cause resistance to single agent RAS inhibition.

"The initiation of the RMC-5552 clinical program is the first step in the evaluation of our first-in-class, bi-steric mTORC1 inhibitor as a RAS Companion Inhibitor for the treatment of tumors driven by co-occurring RAS mutations and genomic activation of the mTORC1 pathway, which account for a significant proportion of RAS-addicted cancers," said Steve Kelsey, M.D., president, research and development at Revolution Medicines. "These co-occurring mutations may contribute to resistance to single-agent RAS inhibitors, and the potential to add RMC-5552 to RAS-directed therapies aligns nicely with our strategy of developing rational, biomarker-driven drug combinations that can achieve maximum clinical benefit in patients with RAS-driven cancers. We also look forward to evaluating RMC-5552 in selected indications where mTORC1 is activated independently of RAS."

New Patent Issuance for RMC-5552 and Related Compounds

In additional news regarding the RMC-5552 program, Revolution Medicines reported that the United States Patent and Trademark Office has issued U.S. Patent No. 10,980,889. This patent provides, in part, composition of matter protection for RMC-5552, as well as related compounds in the company’s proprietary series of selective mTORC1 inhibitors.

About mTORC1

The mTOR Complex 1 (mTORC1) is a central node within the mTOR signaling pathway and a critical regulator of metabolism, growth and proliferation in cancer cells. Oncogenic mutations of genes upstream of mTOR, including PI3 kinase, PTEN, and STK11, can drive abnormal activation of mTORC1 and subsequent inactivation of the tumor suppressor 4EBP1. Selective inhibition of mTORC1 to reactivate 4EBP1 is a potential therapeutic strategy for patients with tumors bearing such mutations. These mutations are often co-occurring with RAS mutations in RAS-addicted tumors and combinations of mTORC1 and RAS-targeted inhibitors may be of particular benefit in this context.