On October 28, 2020 Medidata, a Dassault Systèmes Company, reported that the US Food and Drug Administration (FDA) supported the use of a Medidata Synthetic Control Arm in a phase 3 registrational trial in recurrent glioblastoma (rGBM) (Press release, Medidata, OCT 28, 2020, View Source [SID1234569257]). This is a precedent setting acceptance of a hybrid external control (combining synthetic control arm patients with randomized patients) in a phase 3 trial in an indication that previously used traditional randomized controls.

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Medicenna Therapeutics, Corp. (NASDAQ: MDNA, TSX: MDNA), a clinical stage immunotherapy company, will use a hybrid external control arm in a phase 3 registrational trial in recurrent glioblastoma, an aggressive form of brain cancer. The hybrid external control arm will reduce the number of patients required to be assigned to the control therapy in the trial, will provide rigorous scientific data, and will enable speedier development of the product. The phase 2 single arm trial preceding this phase 3 study was also enhanced by a synthetic control arm and estimates of the treatment effects based on the synthetic control arm were part of the briefing information provided to the FDA for justification of the use in phase 3.

"We are pleased with FDA’s acceptance and look forward to creating a highly rigorous scientific comparison to support development of Medicenna’s MDNA55 for recurrent glioblastoma," said Ruthie Davi, vice president, Data Science, Acorn AI by Medidata. "There are no established therapies to prolong life for people suffering with rGBM, so the hybrid external control arm could provide great hope for patients with this disease."

"We are extremely impressed with the Acorn AI team for providing a scientifically rigorous rationale for the design of an innovative registration trial incorporating an external control arm for the treatment of recurrent glioblastoma (rGBM) with MDNA55. Their expertise and collaborative effort with thought leaders was instrumental in demonstrating to the FDA the validity of a well-designed external control in a registration trial," said Fahar Merchant, PhD, president and CEO, Medicenna Therapeutics, Corp. "The FDA’s acceptance of this unique design will expedite completion of the Phase 3 trial in rGBM, allowing earlier access of MDNA55 for a disease with poor prognosis and high unmet need."

Synthetic control arms are formed by carefully selecting patients from historical clinical trials to match the demographic and disease characteristics of the patients treated with the new investigational product. They have great potential to enhance single arm trials and enable more efficient randomized clinical trials in indications where the standard of care therapy is impracticable or unacceptable to patients.

Medidata is a wholly owned subsidiary of Dassault Systèmes, which with its 3DEXPERIENCE platform is positioned to lead the digital transformation of life sciences in the age of personalized medicine with the first end-to-end scientific and business platform, from research to commercialization.

On October 28, 2020 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, reported the pricing of an underwritten public offering of 2,948,718 shares of its common stock at a public offering price of $39.00 per share (Press release, Scholar Rock, OCT 28, 2020, View Source [SID1234569256]). In addition, in lieu of common stock to certain investors, Scholar Rock is offering pre-funded warrants to purchase 2,179,487 shares of its common stock at a purchase price of $38.9999 per pre-funded warrant, which equals the public offering price per share of the common stock less the $0.0001 exercise price per share of each pre-funded warrant. The aggregate gross proceeds to Scholar Rock from this offering are expected to be approximately $200 million, before deducting underwriting discounts and commissions and other estimated offering expenses. In addition, Scholar Rock has granted the underwriters a 30-day option to purchase up to an additional 769,230 shares of common stock at the public offering price per share of the common stock, less the underwriting discounts and commissions. The offering is expected to close on November 2, 2020, subject to the satisfaction of customary closing conditions. All of the shares and pre-funded warrants are being offered by Scholar Rock.

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Scholar Rock intends to use the net proceeds from the offering to advance SRK-015 in Spinal Muscular Atrophy, including costs associated with preparing for and executing clinical trials (including a Phase 3 clinical trial), SRK-181 in cancer immunotherapy, development of its preclinical and discovery programs, as well as for working capital and other general corporate purposes.

J.P. Morgan Securities LLC, Jefferies LLC and Credit Suisse Securities (USA) LLC are acting as joint book-running managers for the offering. BMO Capital Markets Corp. is acting as lead manager for the offering.

The securities described above are being offered by Scholar Rock pursuant to a shelf registration statement on Form S-3 (No. 333-231920) that was declared effective by the Securities and Exchange Commission (SEC) on June 10, 2019. A preliminary prospectus supplement and accompanying prospectus and a free writing prospectus relating to and describing the terms of the offering were filed with the SEC on October 27, 2020 and October 28, 2020, respectively, and are available on the SEC’s website located at www.sec.gov. A copy of the final prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and may be obtained, when available, by contacting: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at 1-866-803-9204 or by email at [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at 877-547-6340 or by email at [email protected]; or Credit Suisse Securities (USA) LLC, Attention: Prospectus Department, 6933 Louis Stephens Drive, Morrisville, NC 27560, by telephone at (800) 221-1037 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that state or jurisdiction.

On October 28, 2020 Verastem, Inc. (Nasdaq:VSTM) (also known as Verastem Oncology), a biopharmaceutical company committed to advancing new medicines for patients battling cancer, reported new data have been published today in The Lancet Oncology (Press release, Verastem, OCT 28, 2020, View Source [SID1234569255]). The study evaluated the intermittent dosing schedule of VS-6766 (formerly known as CH5126766) to inform further testing of VS-6766 as both a single agent in RAS/RAF-mutant cancers such as KRAS mutant non-small cell lung cancer (NSCLC) or in combination with small molecules including the FAK inhibitor defactinib in KRAS mutant solid tumors (NCT03875820). In this dose-escalation study, tolerability and antitumor activity were observed across various cancers with RAS/RAF/MEK pathway mutations.

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"The positive results observed with this innovative intermittent dosing regimen of VS-6766 demonstrate its significant potential across various cancers with RAS/RAF/MEK pathway mutations," stated Udai Banerji, Professor of Molecular Cancer Pharmacology at The Institute of Cancer Research, London, and Honorary Consultant in Medical Oncology, MBBS, MD, DNB, PhD, FRCP at The Royal Marsden NHS Foundation Trust, London, and lead investigator of the clinical study. "We were encouraged by the data, demonstrating both antitumor activity and tolerability of VS-6766, and this intermittent schedule can be used alone or for combination therapy schedules with other anticancer agents for a variety of difficult-to-treat cancers."

The full manuscript, titled "Intermittent schedules of the oral RAF–MEK inhibitor CH5126766/VS-6766 in patients with RAS/RAF-mutant solid tumours and multiple myeloma: a single-centre, open-label, phase 1 dose-escalation and basket dose-expansion study," can be accessed here.

"These results support the potential of VS-6766 as a treatment for a variety of cancers where conventional approaches have been sub-optimal and there is significant unmet need. We believe VS-6766 has the potential to be the backbone of RAS therapy by addressing the multiple points of resistance and toxicity issues that have made advancing new options difficult," said Brian Stuglik, Chief Executive Officer of Verastem Oncology. "Our Phase 2 registration-directed trials with VS-6766 in low grade serous ovarian cancer and KRAS mutant NSCLC are scheduled to begin by the end of this year. These adaptive design trials are a capital efficient approach to rapidly evaluate VS-6766 alone or in combination with defactinib to determine which regimen to take forward into the expansion phase of the trial."

Results from the Phase 1 Study Investigating Intermittent Dosing of VS-6766 in Patients with RAS/RAF-mutated Solid Tumors and Multiple Myeloma

Between June 2013 to January 2019, 58 patients, including 51 patients with solid tumors and seven patients with multiple myeloma, were enrolled in a study conducted at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital in the U.K. The study consisted of two parts; 1) dose escalation part to determine the recommended dosage (29 patients) and 2) basket expansion part to investigate efficacy and safety of the recommended dosage determined in the dose escalation part (29 patients).

Four mg twice weekly was established as the recommended Phase 2 dose for VS-6766 monotherapy and was deemed tolerable based on clinician’s assessment with several patients remaining on study for more than six months.

In the subsequent basket expansion part, seven (26.9%) of 26 response-evaluable patients with RAS mutations in the basket expansion achieved objective responses, with response rates in patients with NSCLC, gynecological malignancies, colorectal cancer (CRC), melanoma, and multiple myeloma being 3/10 (30%), 3/5 (60%), 0/4 (0%), 0/1 (0%), and 1/6 (16.7%), respectively. In all six responders with solid tumors, tumor shrinkage was observed at the time of the first restaging scan after two cycles of treatment, with partial responses confirmed after two to four cycles. Five of the six responses lasted more than six months.

Among the 57 safety-evaluable patients, the most common Grade 3/4 treatment related adverse events (TRAEs) were rash (19%), CPK elevation (11%), hypoalbuminemia (11%), and fatigue (7%). Five (9%) patients experienced treatment-related serious adverse events. In the study, TRAEs were manageable, resolved spontaneously or reversed with dose modification. There were no treatment-related deaths. The study also confirmed a long half-life of 55 hours and target engagement in the form of reduction of both p-ERK and p-MEK in three patients who underwent paired biopsies, supporting intermittent dosing schedules.

This study was supported by Chugai Pharmaceutical Co., Ltd. Verastem in-licensed VS-6766 from Chugai in January 2020.

About VS-6766

VS-6766 (formerly known as CH5126766 and CKI27) is a unique inhibitor of the RAF/MEK signaling pathway. In contrast to other MEK inhibitors in development, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors.

About Defactinib

Defactinib (VS-6063) is an oral small molecule inhibitor of FAK and PYK2 that is currently being evaluated as a potential combination therapy for various solid tumors. The Company has received Orphan Drug designation for defactinib in ovarian cancer and mesothelioma in the US, EU and Australia. Preclinical research by Verastem Oncology scientists and collaborators at world-renowned research institutions has described the effect of FAK inhibition to enhance immune response by decreasing immuno-suppressive cells, increasing cytotoxic T cells, and reducing stromal density, which allows tumor-killing immune cells to enter the tumor.1,2

About the VS-6766/Defactinib Combination

RAS mutant tumors are present in 30% of all human cancers and have historically presented a difficult treatment challenge and are often associated with significantly worse prognosis. Challenges associated with identifying new treatment options for these types of cancers include resistance to single agents, identifying tolerable combination regimens with MEK inhibitors and new RAS inhibitors in development addressing only a minority of all RAS mutated cancers.

The combination of VS-6766 and defactinib has been found to be clinically active in patients with KRAS mutant tumors. In an ongoing investigator-initiated Phase 1/2 FRAME study, the combination of VS-6766 and defactinib is being evaluated in patients with LGSOC, KRAS mutant NSCLC and colorectal cancer (CRC). Updated interim data from this study presented at the 2nd Annual RAS-Targeted Drug Development Summit in September 2020 demonstrated a 56% overall response rate and long duration of therapy among patients with KRAS-G12 mutant LGSOC. Based on an observation of higher response rates seen in NSCLC patients with KRAS-G12V mutations in the study, Verastem will also be further exploring the role of VS-6766 and defactinib in KRAS-G12V NSCLC. The FRAME study was expanded in August 2020 to include new cohorts in pancreatic cancer, KRAS mutant endometrial cancer and KRAS-G12V NSCLC.

On October 28, 2020 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that data from the IMerge Phase 2 trial were published in the Journal of Clinical Oncology (Press release, Geron, OCT 28, 2020, View Source [SID1234569253]). The article entitled, "Imetelstat Achieves Meaningful and Durable Transfusion Independence in High-Transfusion Burden Patients with Lower Risk Myelodysplastic Syndromes Patients in a Phase 2 Study," is available online. The publication includes data from all 57 patients enrolled in the trial as well as data for the 38-patient target patient population previously reported at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in June 2020.

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"We are pleased that the IMerge Phase 2 data have been published in one of the most prestigious oncology journals, the Journal of Clinical Oncology, and we believe that the publication of these data in JCO represents an increased level of interest from the oncology community"

"With a median duration of 21 months, the durability of transfusion independence observed with imetelstat in the IMerge Phase 2 trial is a clinically meaningful outcome for patients," said David Steensma, M.D., Edward P. Evans Chair in Myelodysplastic Syndromes Research at the Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School, and lead author of the article. "In addition, the reduction in malignant clone size during imetelstat treatment suggests potential disease-modifying activity, which also could be meaningful from a clinical perspective. The adverse event pattern observed in this trial was similar to previous studies of this drug."

The publication reports efficacy, safety and biomarker results from the IMerge Phase 2 clinical trial. As stated in the paper, imetelstat treatment produced meaningful and durable transfusion independence (TI). TI was consistently observed across different patient subgroups, including ring sideroblast positive (RS+) and RS-, as well as high and very high transfusion burdened patients. The data also suggest potential disease-modifying activity with imetelstat by reducing the malignant clones driving the disease. In the IMerge Phase 2, no new safety signals were identified, and the most frequent treatment emergent adverse events were cytopenias, which were reversible and with limited clinical consequence.

"We are pleased that the IMerge Phase 2 data have been published in one of the most prestigious oncology journals, the Journal of Clinical Oncology, and we believe that the publication of these data in JCO represents an increased level of interest from the oncology community," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "The depth and breadth of transfusion independence achievable with imetelstat treatment, as seen in the IMerge Phase 2, can address the significant anemia burden for lower risk MDS patients. These data support our ongoing registration-enabling IMerge Phase 3 clinical trial in lower risk MDS being conducted at multiple sites around the world, and we are planning for top-line results in the second half of 2022."

Ongoing IMerge Phase 2/3 Clinical Trial

The IMerge Phase 2/3 trial is a two-part clinical trial of imetelstat in transfusion dependent patients with Low or Intermediate-1 risk, also referred to as lower risk myelodysplastic syndromes (MDS), who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The primary endpoint is the rate of red blood cell (RBC) transfusion independence (TI) for any consecutive period of eight weeks or longer, or 8-week RBC-TI rate. Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks, or 24-week RBC-TI rate, and the rate of hematologic improvement-erythroid (HI-E), defined as a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden.

The IMerge Phase 2 was an open label, single arm trial to assess the safety and efficacy of imetelstat of a 7.5 mg/kg dose of imetelstat administered as an intravenous infusion every four weeks. The Phase 2 enrolled 57 patients, of which a target patient population of 38 patients were naïve to treatment with a hypomethylating agent (HMA) or lenalidomide and did not have a deletion 5q chromosomal abnormality (non-del(5q)). The IMerge Phase 2 is no longer enrolling patients and patients remaining in the treatment phase continue to receive imetelstat treatment, per investigator discretion.

The IMerge Phase 3 is a double-blind, randomized, placebo-controlled clinical trial with registration intent. The trial is designed to enroll approximately 170 patients with lower risk transfusion dependent MDS who meet the defined target patient population identified in the Phase 2 portion of the trial. The IMerge Phase 3 is currently enrolling patients.

About Myelodysplastic Syndromes

MDS is a group of blood disorders in which the proliferation of malignant progenitor cells produces multiple malignant cell clones in the bone marrow resulting in disordered and ineffective production of the myeloid lineage, which includes red blood cells, white blood cells and platelets. Chronic anemia is the predominant clinical problem in patients who have lower risk MDS. Many of these patients become dependent on red blood cell transfusions due to low hemoglobin. Serial red blood cell transfusions can lead to elevated levels of iron in the blood and other tissues, which the body has no normal way to eliminate. Iron overload is a potentially dangerous condition. Studies in patients with MDS have shown that iron overload resulting from regular red blood cell transfusions is associated with lower quality of life, shorter overall survival and a higher risk of developing acute myeloid leukemia.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Early clinical data suggest imetelstat may have disease-modifying activity through the apoptosis of malignant stem and progenitor cells, which allows potential recovery of normal hematopoiesis. Geron’s imetelstat development program includes two ongoing or planned registration-enabling studies, IMerge, an ongoing Phase 2/3 clinical trial in lower risk myelodysplastic syndromes (MDS), and a planned Phase 3 clinical trial in refractory myelofibrosis (MF) expected to be open for patient screening and enrollment in the first quarter of 2021. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.

On October 28, 2020 Quanterix Corporation (NASDAQ: QTRX), a company digitizing biomarker analysis to advance the science of precision health, reported that its Chairman, Chief Executive Officer and President and Founder, Powering Precision Health (PPH), Kevin Hrusovsky, will speak today at the Precision Medicine Leaders Summit’s (PMLS) Precision Oncology Conference (Press release, Quanterix, OCT 28, 2020, View Source [SID1234569252]). Hrusovsky’s keynote presentation, "Revolutionizing Cancer Treatment and Detection with Biomarkers," will take place at 3:15 p.m., EDT. To register for today’s event visit, View Source

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During his presentation, Hrusovsky will discuss advances in highly sensitive multiplex assays, which are enabling researchers to identify and quantify multiple oncology biomarkers simultaneously. This insight paired with the unprecedented ability to see biomarkers in minute concentrations in the blood, as enabled by ultra-sensitive biomarker platforms, is creating new pathways for detecting cancer at its earliest stages. Hrusovsky’s keynote will also speak to the important role of biomarkers in improving the efficacy and safety of immuno-oncology-based treatments by empowering researchers to optimize dosing and minimize toxicity associated with severe side effects.