On October 28, 2020 Nektar Therapeutics (Nasdaq: NKTR) reported that it will announce its financial results for the third quarter 2020 on Thursday, November 5, 2020, after the close of U.S.-based financial markets. Howard Robin, President and Chief Executive Officer, will host a conference call to review the results beginning at 5:00 p.m. Eastern Time/2:00 p.m. Pacific Time (Press release, Nektar Therapeutics, OCT 28, 2020, View Source [SID1234569260]).

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The press release and live audio-only webcast of the conference call can be accessed through a link that is posted on the Home Page and Investors section of the Nektar website: View Source The web broadcast of the conference call will be available for replay through Tuesday, December 1, 2020.

On October 28, 2020 Asieris Pharmaceuticals, a China-based biotech company specializing in the development and commercialization of new drugs for the treatment of genitourinary tumors and related diseases, reported that Australian regulatory authorities have approved its Phase I clinical trial of APL-1501 (Press release, Asieris Pharmaceuticals, OCT 28, 2020, View Source [SID1234569258]). The objective of this Phase I study is to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of APL-1501.

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APL-1501, which is independently developed by the Prodrug Accurate Drug Delivery (PADD) platform of Asieris, is an oral sustained-release product based on APL-1202 and will be the second generation product of APL-1202 to support new clinical development globally. APL-1501 inherits the unique oral administration of APL-1202 and the druggability of APL-1501 is improved by the design of prodrug molecules. Based on these, APL-1501 can improve patient compliance by reducing medication frequency, combined with the sustained-release technology which can contribute to controlled drug release and lengthen the drug plasma exposure time. APL-1501 has better pharmacokinetic (PK) characteristics so that this product is expected to not only treat bladder cancer, but also for other diseases such as prostate cancer, urinary tract infection, etc. Since APL-1501 is a product developed by Asieris independently, a comprehensive global intellectual property rights strategy has been developed to provide strong support for product life cycle managment and global expansion.

APL-1202 is being developed as a new drug of Asieris for the treatment of non-muscle invasive bladder cancer (NMIBC). It is the first oral and reversible methionine aminopeptidase II type (MetAP2) inhibitor currently under Phase III clinical development in the world. APL-1202 finished patient enrollment in pivotal registration trial in China in 2019. APL-1202 also completed the Phase I clinical trial in the US. Currently, the standard treatment of NMIBC is a Trans-Urethral Resection of Bladder Tumor (TURBT). Because of a high tumor recurrence rate after TURBT, intravesical chemo- or immune-therapies are required after the procedure. At present, choice of second-line treatment for relapsed patients is very limited. A radical cystectomy is the standard treatment for recurring high-risk NMIBC patients. No oral drugs have been approved for NMIBC to date.

"The approval of APL-1501 clinical trial in Australia is another important milestone on the journey of Asieris’ international clinical development", commented Dr. Kevin Pan, founder and CEO of Asieris. "As the second generation product of APL-1202, APL-1501 will bring better treatment choice to patients and reduce the pain and adverse reactions. Asieris will continue to adhere to the vision of ‘We strive for healthy and dignified lives’. We hope the innovative products will benefit more patients globally soon."

About APL-1501 and APL-1202

APL-1501 is developed by Asieris from its PADD technology platform as the second generation product of APL-1202, which has better pharmacokinetic characteristics. Besides the treatment of NMIBC, the product is expected to enter more therapeutic fields for clinical development, such as prostate cancer, urinary tract infection, etc.

APL-1202 is being developed as a new drug of Asieris for the treatment of non-muscle invasive bladder cancer (NMIBC) and is the first oral and reversible methionine aminopeptidase II type (MetAP2) inhibitor currently under Phase III clinical development in the world. In preclinical studies, APL-1202 has demonstrated both anti-angiogenic and anti-tumor activities as well as a potential synergistic effect with anti-BCG or epirubicin. APL-1202 is currently under clinical investigation for multiple indications. The treatment regimen with APL-1202 is convenient and well-tolerated, without causing pain or injury to the urethra, and may help some high-risk patients avoid radical cystectomy.

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.