On August 18, 2023 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported topline results from LITESPARK-005, the first positive Phase 3 trial investigating WELIREG, Merck’s oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor (Press release, Merck & Co, AUG 18, 2023, View Source [SID1234634501]). LITESPARK-005 is evaluating WELIREG for the treatment of adult patients with advanced renal cell carcinoma (RCC) that has progressed following PD-1/L1 checkpoint inhibitor and vascular endothelial growth factor-tyrosine kinase inhibitor (VEGF-TKI) therapies. In the trial, WELIREG showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to everolimus, based on a pre-specified interim analysis conducted by an independent Data Monitoring Committee. A statistically significant improvement in the trial’s key secondary endpoint of objective response rate (ORR) was also demonstrated. A trend toward improvement in overall survival (OS), a dual primary endpoint, was observed; however, this result did not reach statistical significance. OS will be tested at a subsequent analysis. The safety profile of WELIREG in this trial was consistent with that observed in previously reported studies. Results will be presented at an upcoming medical meeting and shared with regulatory authorities.

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"Patients with advanced RCC face low survival rates, and for those whose cancer progresses following PD-1/L1 and VEGF-TKI therapies, there is a need for new treatment options that can reduce their risk of disease progression or death," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. "This is the first Phase 3 trial to show positive results in advanced RCC following these therapies and the first new mechanism to demonstrate potential in advanced RCC in recent years. We look forward to discussing these results with health authorities."

WELIREG was the first HIF-2α inhibitor therapy approved in the U.S. and is currently approved in the U.S., Great Britain, Canada and several other countries for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery, based on ORR and duration of response (DOR) data from the Phase 2 LITESPARK-004 trial. Additional applications are currently under regulatory agency review worldwide based on LITESPARK-004.

LITESPARK-005 is part of a comprehensive development program for WELIREG comprised of four Phase 3 trials in RCC, including LITESPARK-011 and LITESPARK-012, evaluating WELIREG in the second-line and treatment-naïve advanced disease settings, and LITESPARK-022, evaluating WELIREG in the adjuvant setting.

About LITESPARK-005

LITESPARK-005 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT04195750) evaluating WELIREG compared to everolimus for the treatment of patients with advanced RCC that has progressed after prior treatment with PD-1/L1 and VEGF-TKI therapies, in sequence or in combination. The dual primary endpoints are PFS and OS. Secondary endpoints include ORR, DOR and safety and tolerability. The trial enrolled 746 patients who were randomized to receive WELIREG (120 mg orally once daily) or everolimus (10 mg orally once daily).

About renal cell carcinoma

Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCCs. Renal cell carcinoma is about twice as common in men than in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. In the U.S., approximately 15% of patients with kidney cancer are diagnosed at an advanced stage.

About WELIREG (belzutifan) 40 mg tablets, for oral use
Indication in the U.S.

WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.

Selected Safety Information for WELIREG
Warning: Embryo-Fetal Toxicity

Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception as WELIREG can render some hormonal contraceptives ineffective.

Anemia

WELIREG can cause severe anemia that can require blood transfusion. In Study 004, anemia occurred in 90% of patients and 7% had Grade 3 anemia. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, anemia occurred in 76% of patients and 28% had Grade 3 anemia.

Monitor for anemia before initiation of and periodically throughout treatment. Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers due to potential increases in exposure that may increase the incidence or severity of anemia.

Transfuse patients as clinically indicated. For patients with hemoglobin (Hb) <9g/dL, withhold WELIREG until Hb≥9g/dL, then resume at reduced dose or permanently discontinue depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until Hb ≥9g/dL, then resume at a reduced dose or permanently discontinue.

The use of erythropoiesis stimulating agents (ESAs) for treatment of anemia is not recommended in patients treated with WELIREG.

Hypoxia

WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. In Study 004, hypoxia occurred in 1.6% of patients. In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, hypoxia occurred in 29% of patients; 16% were Grade 3 hypoxia.

Monitor oxygen saturation before initiation of and periodically throughout treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider.

Embryo-Fetal Toxicity

Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman.

Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Adverse Reactions

In Study 004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each).

WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each).

Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness.

Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%).

The most common adverse reactions (≥25%) were decreased hemoglobin (93%), anemia (90%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%).

In Study 001, a clinical trial in patients with advanced solid tumors (n=58) treated at the recommended dose, the following additional adverse reactions have been reported: edema, cough, musculoskeletal pain, vomiting, diarrhea, and dehydration.

Drug Interactions

Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended.

Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding.

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose.

Females and Males of Reproductive Potential

WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG.

Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose.

Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown.

Pediatric Use

Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established.

On August 18, 2023 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported that on August 17, 2023 (the "Date of Grant"), the Company approved the grant of inducement stock options covering an aggregate of 107,250 shares of Iovance’s common stock to eight new non-executive employees (Press release, Iovance Biotherapeutics, AUG 18, 2023, View Source [SID1234634499]).

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The awards were granted under Iovance’s 2021 Inducement Plan, which was adopted on September 22, 2021 and amended on January 12, 2022 and May 10, 2023, and provides for the granting of equity awards to new employees of Iovance by the Company’s compensation committee in accordance with Nasdaq Listing Rule 5635(c)(4). Each of the stock options granted as referenced in this press release has an exercise price of $6.27, the closing price of Iovance’s common stock on the Date of Grant. Each stock option vests over a three-year period, with one-third of the shares vesting on the first anniversary of the employee’s start date (referred to as the "First Vesting Date"), and the remaining shares vesting in eight quarterly installments over the next two years, commencing with the first quarter following the First Vesting Date, subject to continued employment with the Company through the applicable vesting dates.

On August 18, 2023 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported that in connection with the hiring of Kevin Brodbeck, Senior Vice President and Chief Technical Officer, the Compensation Committee of Deciphera’s Board of Directors approved the grant of a stock option to purchase 89,200 shares of Deciphera’s common stock, 44,600 restricted stock units ("RSUs") and a special grant of 15,000 RSUs ("Special RSUs") to Mr. Brodbeck with a grant date of August 15, 2023 (Press release, Deciphera Pharmaceuticals, AUG 18, 2023, View Source [SID1234634498]).

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The equity awards were granted under the Company’s 2022 Inducement Plan and were made pursuant to Nasdaq Listing Rule 5635(c)(4). The grants were an inducement material to Mr. Brodbeck accepting employment with the Company. The options have a ten-year term, and the exercise price of the options is $15.48, equal to the fair market value of the Company’s common stock on the Nasdaq on August 15, 2023. The shares subject to the option vest over a four-year period, with 25 percent of the shares subject to the option vesting on the first anniversary of Mr. Brodbeck’s date of hire and the remainder vesting in equal monthly installments over three years thereafter. The 44,600 shares underlying the RSU grant will vest in equal annual installments over a three-year period, beginning on or about the one-year anniversary of the grant date. The 15,000 shares underlying the special grant vest over a two-year period, with 50 percent vesting on the first anniversary of Mr. Brodbeck’s date of hire and the remainder vesting on or about the two-year anniversary of the grant date. The awards are subject to the terms and conditions of their applicable equity award agreements, including having a continued relationship with the Company on the vesting date.

On August 18, 2023 Imugene Limited (ASX:IMU) (Company), a clinical stage immuno-oncology company, reported that it has received firm commitments from institutional and sophisticated investors for a $35 million placement (Placement Subscribers) of approximately 416.7m new fully paid ordinary shares (New Shares) in the Company at a price of $0.084 per share (Placement) (Press release, Imugene, AUG 18, 2023, View Source [SID1234634487]).

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The Placement received strong interest and support from specialist biotech institutional investors, as well as a number of the Company’s Directors and key management personnel who have committed approximately $840,000 (part of which shall be subject to shareholder approval at an extraordinary general meeting to be convened by the Company shortly).

The Placement is being followed by a share purchase plan (SPP), to raise approximately $30 million, for existing eligible shareholders (Eligible Shareholders) at the lower of $0.084 and a 2.5% discount to the 5-day VWAP up to and including the closing date of the SPP.

Under the Placement and SPP (together, the Offer), Placement Subscribers and Eligible Shareholders are anticipated to receive one free option for every New Share (New Options) subscribed for under the Offer (Options Offer). The New Options will have an exercise price of $0.118 per option with an expiration of 31 August 2026 and will be subject to shareholder approval. It is intended that the New Options will be quoted on the ASX. The funds raised from the Offer will be used:
 to make the upfront payment of US$8 million to Precision Biosciences Inc. (NASDAQ GS: DTIL) in accordance with the terms of the licence agreement entered into between the Company and Precisions Biosciences Inc. on 16 August 2023 (Licence Agreement);
 to meet the deferred consideration and milestone payment obligations under the Licence Agreement, including for the completion of the Phase 1b clinical trial for the licensed Azer-cel Allogeneic CD19 Car-T technology; and
 for associated manufacturing, clinical trial, regulatory and working capital costs relating to the Licence Agreement.

Further details in relation to the Licence Agreement can be found in the Company’s announcement dated 16 August 2023. In relation to the Offer, Imugene Founder and Executive Chairman Paul Hopper said: "I am delighted with the very strong support shown for the raise with institutional interest coming from Australia, Asia in particular, and the US. It was very important to the Board that our loyal individual shareholders be offered the opportunity to also participate via the SPP, and we are glad to say that their voice has been heard". Imugene Managing Director and CEO Leslie Chong said: "We appreciate the strong support and belief from new and existing investors in our Company’s vision. This raise places Imugene in an enviable position with regards to its balance sheet with the financial horsepower to execute across all our platforms. I thank all our investors for the confidence they have shown in our company." Bell Potter Securities Limited is acting as Lead Manager to the capital raising.

OFFER

About the Placement

Under the terms of the Placement, the Company has secured commitments of $35 million and proposes to issue a total of 416,666,667 New Shares to Placement Subscribers at a price of $0.084 per share, representing a discount of 10.64% to the last close on Tuesday, 15 August 2023 ($0.094), and a discount of 12.38% to the 20-day VWAP up to, and including, Tuesday, 15 August 2023 ($0.096). The Placement is being conducted under Imugene’s existing placement capacity pursuant to ASX Listing Rule 7.1, save for those commitments by certain Directors and will be subject to prior shareholder approval.

About the SPP

The Company will also offer a SPP to Eligible Shareholders at a price equal to the lower of:  $0.084 (being the same price as for the Placement); and  a 2.5% discount to the 5-day VWAP up to and including the closing date of the SPP. Under the SPP, Eligible Shareholders listed on the Imugene register at 7:00pm (Sydney time) on the record date of Thursday, 17 August 2023 with an address in Australia or New Zealand will be offered the opportunity to apply for up to $30,000 of fully paid ordinary New Shares in Imugene, without incurring brokerage fees or other transactions costs, irrespective of their holding size. The SPP is not underwritten.

Notwithstanding the target raise amount of $30 million, the Company reserves its right to increase or decrease the amount to be raised under the SPP. Any funds raised in excess of the target raise amount would also be used to fund the development of the CAR T drug Azer-Cel technology and associated costs relating to the Licence Agreement. The SPP shares will be issued pursuant to Exception 5 in ASX Listing Rule 7.2 and will not count towards Imugene’s placement capacity.

About the Options Offer

Under the Offer, Imugene intends to issue one free attaching New Option for every New Share subscribed for by Placement Subscribers and Eligible Shareholders under the SPP, for an aggregate of approximately 773.9m New Options to be issued. The New Options will have an exercise price of $0.118, and will expire on 31 August 2026. The offer for New Options will be set out in a prospectus (Prospectus) and the issuance of the New Options will be subject to shareholder approval at an extraordinary general meeting to be convened shortly.

Other information
The SPP (and Options Offer) will be made under a transaction specific Prospectus which is anticipated to be lodged with ASIC in accordance with the above timetable. Eligible Shareholders should carefully consider the Prospectus before deciding to apply under the SPP. Eligible Shareholders who wish to participate in the SPP will need to
complete the personalised application form (Application Form).

All dollar references are to the Australian dollar unless otherwise stated.

On August 17, 2023 TFC Therapeutics (TFC), a biotechnology company focused on developing novel biologics to target and eliminate key drivers of cancer recurrence and metastasis, reported a financing led by ARCH Venture Partners with participation from Breakout Ventures, Alexandria Real Estate Equities, and Alumni Ventures (Press release, TFC Therapeutics, AUG 17, 2023, View Source [SID1234634492]). In connection with the financing, Steven Gillis, Ph.D., Managing Director at ARCH, has been appointed as Chairman of the TFC Board of Directors.

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TFC has entered into an exclusive license agreement with Columbia University to develop a drug discovery platform that targets Tumor Macrophage Hybrid (TMH) cells. Under the terms of the agreement, TFC has the exclusive rights to develop and commercialize intellectual property developed at Columbia University by Azra Raza, Chan Soon-Shiong Professor of Medicine and Clinical Director of the Edward P. Evans Foundation Myelodysplastic Syndrome Center at Columbia University Vagelos College of Physicians and Surgeons, and Abdullah Ali, PhD, Assistant Professor of Medical Sciences (in Medicine) at Columbia University Vagelos College of Physicians and Surgeons.

TFC is focused on developing therapies to eliminate the most resilient cancers and stop disease recurrence. TFC’s emerging platform technologies are focused on the elimination of TMH cells, which are found in the bloodstream of patients with cancer. The presence of TMH cells in the circulation of cancer patients is associated with metastasis, resistance to traditional therapies, relapse, and poor outcomes. In animal models, these cells have been associated with metastasis and resistance to standard therapies.

"TFC is positioned to help patients fight cancer and overcome resistance to current therapies by developing biologics designed to target and eliminate a specific cell-type that may play a fundamental and causative role in metastasis and cancer recurrence," said Dr. Gillis. "Despite substantial R&D efforts and regulatory approvals of more anti-cancer therapies, new approaches to therapy are still sorely needed. I look forward to the results of ongoing work at TFC and hope that its efforts result in the development of a new and important means of therapy for cancer patients."

"At TFC, we remain committed to bringing forward a new approach to treatment of cancer metastasis and relapse that will benefit patients living with cancer," said Jennifer Power, Chief Executive Officer of TFC Therapeutics. "We believe that targeting a key driver of cancer, TMH cells, coupled with the financial support of our investor syndicate and the scientific acumen of our founders, gives TFC a significant advantage in building a valuable platform, pipeline and company."

TFC Leadership

The TFC team has deep experience in the development and commercialization of novel medicines. TFC’s Chief Executive Officer, Jennifer Power, is an experienced leader with over 20 years of experience in the development, commercialization, and delivery of medicines. Prior to joining TFC, Ms. Power was Deputy Director, Innovation Introduction at the Bill & Melinda Gates Foundation. Prior to that, she spent twelve years at Pfizer, Inc. where she served in multiple senior roles, leading strategic marketing and delivery of multi-billion-dollar drug portfolios. Ms. Power serves as an Advisory Board Member, Global Health JSC at Antiva Bioscience, Inc. Ms. Power received her MBA from Columbia University and her BA in Economics from Pomona College.