On September 20, 2022 ATOMIC reported that Retrospective data showed how common central nervous system metastases are among patients with non-small cell lung cancer and ALK or ROS1 alterations who have been treated with tyrosine kinase inhibitors (Press release, ATOMIC, SEP 20, 2022, View Source;utm_medium=rss&utm_campaign=industry-news-brain-mri-surveillance-needed-for-tkl-treated-alk-or-ros7-positive-nsclc [SID1234623183]).

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"I’m really excited about this study because it’s a collaboration between 12 sites across North America, including one in Canada," Melina Marmarelis, MD, assistant professor of medicine at University of Pennsylvania remarked about a presentation from the ASCO (Free ASCO Whitepaper) Annual Meeting. "It’s a retrospective cohort study of patients with ALK and ROS1 alterations in non-small cell lung cancer. It’s one of the biggest retrospective studies out there."

Academic Thoracic Oncology Medical Investigators ConsortiumThe study collaborators came from 12 Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC) sites.

"This is a cohort of patients starting in 2003 all the way to 2021," Marmarelis said. "This will allow us to really look at treatment patterns and the effect of sequential therapies, in particular, on things like brain metastases."

The final analyses included 566 patients with ALK (n = 464) and ROS1 (n = 102) alterations. In the ALK group, 92% (n = 426) received a TKI at some point during therapy and 86% (n = 88) in the ROS1 group. TKI was first line therapy for 262 patients with the ALK alteration and for 48 patients with ROS1.

The most common first line TKI was crizotinib (Xalkori, Ffizer) for both ALK and ROS1 alterations, followed by alectinib (Alecensa, Genetech) for ALK and lorlatinib (Lorbrena, Pfizer) for ROS1. The second most common initial TKI was alectinib for ALK and entrectinib (Rozlytrek, Genentech) for ROS1. For patients with ALK alterations, the median follow-up time was 31.1 (95% CI, 27.6-35) months and 32.6 (95% CI, 25.7-39.6) months for patients with ROS1 alterations.

According to the abstract, the median overall survival from start of the first TKI was 53.3 months for ALK alterations ( 95% CI, 40-68.9) and 42 months for ROS1 alterations ( 95% CI, 31.8-not reached). Prior to receiving first line therapy, 321 patients had available brain imaging. Of these patients, 40% with ALK alterations, (n = 105) and 39% with ROS1 (n = 23) had CNS disease.

"We zeroed in on brain metastases for this presentation and showed that they are still very prevalent among patients with ALK and ROS1 alterations," Marmarelis said. "In particular, with the earlier TKis such as crizotinib, patients are more likely to develop a new brain metastasis while on treatment as opposed to some later-generation TKis."

Among patients without previous CNS disease, brain metastases developed at 24 months in 14.4 % ( 95% CI, 6.1-26.1) of patients in the ALK group who received other TKI’s compared with 48.9% ( 95% CI, ) who received crizotinib. For patients in the ROS1 group, 47.4 % ( 95% CI, 27.9-64.6) developed brain metastases at 24 months. Treatment discontinuation of first TKI occurred a median 11.2 months for ALK alteration and 10.8 months for ROS1.

"What this really shows is that even with later-generation TKis, brain metastases are common and routine surveillance with brain MRis should be included in the treatment of these patients," Marmarelis concluded.

Source: Marmarelis, ME, et al. Treatment patterns and outcomes in ALK or ROS1 altered NSCLC: An ATOMIC Registry Study. Presented at: ASCO (Free ASCO Whitepaper) Annual Meeting; June 3-7, 2022; Chicago.

Acknowledgements: Helio.com / HemOnc Today, by Marley V. Ghizzone

On October 20, 2022 SYnAbs reported a research collaboration program to discover novel therapeutic antibodies against challenging G Protein Coupled Receptor (GPCR) targets (Press release, Domain Therapeutics, SEP 20, 2022, View Source [SID1234622452]).

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For Domain Therapeutics, this collaboration aims at diversifying its proprietary portfolio of immunotherapies with biologics to deliver therapeutic solutions against tumors triggering GPCR-mediated immunosuppression. Under the terms of the agreement, Domain Therapeutics retains exclusive worldwide rights to validate, optimize, develop and commercialize any therapeutic antibodies discovered in the course of the collaboration.

For SYnAbs, the goal is to further optimize its technologies capable of generating highly specific antibodies targeting epitopes that are difficult to express in their native and functionally active conformation.

SYnAbs approach consists in immunizing species with peptides and its proprietary syngeneic cell lines, all mixed with its in-house adjuvant in order to neutralize the immunotolerance usually developed against highly homologous transmembrane targets and benefit from a natural in-vivo maturation.

SYnAbs is also the developer of the rat-LOU species, a species known to be a high responder against haptens and which has the unique ability to naturally generate autoantibodies. This animal is already the source of several therapeutic antibodies such as Siplizumab (licensed to MedImmune, Phase III), LO-CD2b (Preclinical Tox), LO-TACT- 1, anti-CD25 (Phase I/II) and more recently SYnC3aR, a blocking mAb to hC3aR anaphylatoxin receptor.

Under the terms of the agreement, SYnAbs will utilize its know-how and proprietary technologies combined with Domain Therapeutics deep expertise in GPCRs and immuno-oncology to identify novel high-potential drug candidates. Domain will be responsible for the preclinical and clinical development of the jointly discovered antibodies and for a potential partnership with a third party company according to Domain Therapeutics strategy.

On September 20, 2022 Alpine Immune Sciences, Inc. (the "Company") and Cowen and Company, LLC ("Cowen") reported that mutually terminated the Sales Agreement (the "Sales Agreement") between the parties dated July 2, 2021 (Filing, 8-K, Alpine Immune Sciences, SEP 20, 2022, View Source [SID1234621331]). The Sales Agreement provided that the Company may sell shares of its common stock, from time to time, for up to $75,000,000 in aggregate sales proceeds, through an "at the market" equity offering program under which Cowen acted as sales agent. No shares of the Company’s common stock were sold under the Sales Agreement that has been terminated.

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The foregoing description of the Sales Agreement is not complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is filed as Exhibit 1.1 to the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission (the "SEC") on July 2, 2021.

On September 20, 2022 Verismo Therapeutics, a clinical-stage biotechnology company and a Penn-spinout behind the novel KIR-CAR platform technology, reported that is has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a first-in-human Phase 1 clinical trial of SynKIR-110 (Press release, Verismo Therapeutics, SEP 20, 2022, View Source [SID1234619712]).

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The Phase 1 trial, STAR-101 (SynKIR T cell Advanced Research), will assess safety, tolerability, and preliminary efficacy of SynKIR-110 in patients with mesothelin expressing ovarian cancer, cholangiocarcinoma and mesothelioma. This first-in-human trial seeks to address several areas of high unmet medical need. For each indication, the five-year survival rates are 49.7% for ovarian cancer, 30% for cholangiocarcinoma and 10% for mesothelioma. Patients suffering from these diseases urgently need a successful treatment option.

STAR-101 will mark the first-in-human study for SynKIR T cells, a next generation approach to cell therapy targeting solid tumors powered by the KIR-CAR platform. Its unique, multi-chain KIR-CAR construct reduces T cell exhaustion through the natural on-and-off switch that allows the cells to rest when not bound to the tumor, as well as enhanced surface stability to improve the performance of the cells in the harsh microenvironment of solid tumors.

"Pre-clinical data have shown enhanced efficacy in murine models with no additional safety concerns. The FDA’s clearance of our SynKIR-110 IND represents a new chapter for Verismo as we initiate the first-ever clinical trial for KIR-CAR T cells. It also validates the years of innovative research and hard work by industry pioneers at Penn and the Verismo team," said Dr. Bryan Kim, CEO of Verismo.

"SynKIR-110 is the first product to use the novel KIR-CAR platform. Our technology incorporates a natural on/off switch that allows KIR-CAR T cells to rest when not exposed to tumor antigens, as well as providing an enhanced cell-surface stability of the KIR-CAR," said Dr. Laura Johnson, CSO of Verismo. "These enhancements will allow KIR-CAR T cells to better cope with the harsh tumor microenvironment of solid tumors and, potentially, lead to better outcomes for our patients."

Verismo plans to begin enrolling patients in the first quarter of 2023 at the initial clinical site, the Hospital of the University of Pennsylvania.

On September 20, 2022 Shuttle Pharmaceuticals Holdings, Inc. ( Nasdaq: SHPH), a discovery and development stage specialty pharmaceutical company focused on improving the outcomes of cancer patients treated with radiation therapy (RT) while reducing its side effects, reported that it entered into an agreement with TCG GreenChem, Inc. to manufacture Ropidoxuridine, the Company’s lead clinical sensitizer drug candidate, for use in formulating the drug product for testing in clinical trials of Ropidoxuridine and RT of cancers (Press release, Shuttle Pharmaceuticals, SEP 20, 2022, View Source [SID1234619711]).

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"Shuttle Pharma’s platform of sensitizers offers a pipeline of product candidates designed to address the urgent clinical need and the current limitations of using ‘off-label’ drugs with potential new sensitizer agents," said Dr. Anatoly Dritschilo, Chief Executive Officer of Shuttle Pharmaceuticals. "Ropidoxuridine, our lead clinical sensitizer drug candidate, sensitizes rapidly growing cancer cells and selective histone deacetylase (HDAC) inhibitors, to sensitize cancer cells and stimulate the immune system. Our novel technologies will be tested in combination with radiation therapies, such as conventional X-ray and proton radiation therapies, and in combination with immune therapies."

"Today’s agreement with TCG GreenChem allows us to advance our clinical research, including our proposed Phase II clinical trials, to establish the data necessary for the FDA to determine efficacy in treating brain tumors, sarcomas and pancreatic cancers, diseases that offer potential for orphan designations. For instance, the FDA has already granted approval of our application for orphan-drug designation for Ropidoxuridine for the treatment of glioblastoma. We look forward to working with TCG GreenChem to advance our clinical work to improve outcomes for these cancer patients," Dr. Dritschilo concluded.

In conjunction with manufacturing Ropidoxuridine, TCG GreenChem will perform process research, development and optimization work for Shuttle Pharma related to Ropidoxuridine and create working standards of starting materials and intermediates to support the qualitative/quantitative analysis of the drug reaction progress, determination of impurities, total mass balance and assay yields of the reactions. Shuttle Pharma will own all intellectual property and improvements developed through the Manufacturing Agreement.

TCG GreenChem, Inc. was founded by former large pharma pharmaceutical executives with a track record in the development of hundreds of New Chemical Entities into the clinic and commercialization of several well-known pharmaceutical products for Boehringer Ingelheim Pharmaceuticals, Inc., Sepracor, Inc., and Merck & Co, Inc. Dr. Chris Senanayake, the CEO and CSO of TCG GreenChem, CSO of TCG Lifesciences Pvt Ltd., and who serves on the board of directors of Shuttle Pharma, is a pioneering scientist and business executive who recently received two 2022 Business Worldwide Magazine CEO Awards, including "Best CEO in the Pharmaceutical Industry – North America" and the "Growth Strategy CEO of the Year – USA." In addition, he has been recognized as one among the "Top 20 Dynamic CEOs of 2022" in The CEO Publication Magazine. Also, Dr. Joseph D. Armstrong, III, co-founder and COO of TCG GreenChem, and one of the recipients of the Presidential Green Challenge Award, as determined by the EPA, is on Shuttle Pharma’s Scientific Advisory Board. In this capacity, Dr. Armstrong provides insight on green technologies to manufacture and formulate clinical supplies of Ropidoxuridine, to accelerate this molecule rapidly through the drug development pathway to commercialization.

Various sources have estimated that more than 800,000 patients in the US are treated with radiation therapy for their cancers. According to the American Cancer Society about 50% are treated for curative purposes and the balance for therapeutic care. The market opportunity for radiation sensitizers lies with the 400,000 patients treated for curative purposes. The number of patients being treated with RT is expected to grow by more than 22% over the next five years. Based on a rough estimate of a course of radiation sensitizing brand drug therapy (off label at this time) of $12,000 per patient—the market size would be in excess of $4.0 billion.