On September 24, 2021 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported the closing of a public offering of 27,568,072 shares of its common stock, which includes the sale of an additional 4,740,000 shares of its common stock pursuant to the full exercise of the underwriters’ option to purchase additional shares, and of pre-funded warrants to purchase 8,771,928 shares of its common stock (Press release, Leap Therapeutics, SEP 24, 2021, View Source [SID1234590255]). The gross proceeds to Leap from this offering were approximately $104 million, including $7.25 million invested by our collaborator and existing investor BeiGene, Ltd., before deducting underwriting discounts and commissions and other estimated offering expenses payable by Leap.

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Piper Sandler & Co., Raymond James & Associates, Inc. and Mizuho Securities USA LLC acted as book-running managers for the offering. Robert W. Baird & Co. Incorporated acted as lead manager for the offering.

The securities were offered and sold pursuant to an effective shelf registration statement on Form S-3 (File No. 333-248797) that was previously filed by Leap with the Securities and Exchange Commission (the "SEC") on September 14, 2020 and was declared effective by the SEC on October 16, 2020. A final prospectus supplement and the related prospectus have been filed with the SEC and are available for free on the SEC’s website at View Source Copies of the final prospectus supplement and the accompanying prospectus relating to the offering, when available, may also be obtained from Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, MN, 55402, Attention: Prospectus Department, by telephone at (800) 747-3924 or by e-mail at [email protected]. These documents may also be obtained from Raymond James & Associates, Inc., Attention: Equity Syndicate, 880 Carillon Parkway, St. Petersburg, Florida 33716, by telephone at (800) 248-8863, or by e-mail at [email protected]; or from Mizuho Securities USA LLC, Attention: Equity Capital Markets, 1271 Avenue of the Americas, 3rd Floor, New York, NY, 10020, by telephone at (212) 205-7600, or by e-mail at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy 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 any such state or jurisdiction.

On September 24, 2021 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing immune activators to target hard-to-treat solid tumors, reported that the European Patent Office has granted EU Patent no EP3402889 (Press release, Targovax, SEP 24, 2021, View Source [SID1234590250]). The patent covers the use of ONCOS-102 in combination with chemotherapy in malignant pleural mesothelioma.

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Torbjørn Furuseth, Chief Financial Officer of Targovax, said: "We are delighted that this EU patent has been granted, further strengthening Targovax’s intellectual property portfolio. The 24-month data from our ONCOS-102 trial in mesothelioma demonstrates encouraging survival data in this area of large medical need. Securing this patent protects our innovative oncolytic immunotherapy platform and strengthens our future market position."

Targovax’s lead product candidate, ONCOS-102, is a genetically modified oncolytic adenovirus, which has been engineered to selectively infect cancer cells and activate the immune system. In June 2021, the 24-month follow-up in the malignant pleural mesothelioma (MPM) trial showed that median overall survival (mOS) for patients in first-line treatment with ONCOS-102 plus chemotherapy will be between 21.9 and 25.0 months, which is very encouraging in this patient population. For the first-line standard of care (SoC)-only control group mOS is 13.5 months, which is similar to outcomes from previously reported trials where patients received the same chemotherapy treatment. In this open label phase I/II trial, ONCOS-102 has been tested in first and second (or later) line MPM patients to assess safety, immune activation, and clinical efficacy of the combination of ONCOS-102 to SoC chemotherapy (pemetrexed/cisplatin).

Based on these encouraging pre-clinical and clinical effects associated with broad immune activation, the US FDA granted ONCOS-102 Fast Track designation for MPM in February 2021. Targovax has previously received orphan drug designation for MPM in both the US FDA and the European Medicines Agency.

On September 24, 2021 AstraZeneca and MSD reported that Positive high-level results from the PROpel Phase III trial showed it’s Lynparza (olaparib) in combination with abiraterone demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) versus standard-of-care abiraterone as a 1st-line treatment for men with metastatic castration-resistant prostate cancer (mCRPC) with or without homologous recombination repair (HRR) gene mutations (Press release, AstraZeneca, SEP 24, 2021, View Source [SID1234590249]).

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At a planned interim analysis, the Independent Data Monitoring Committee (IDMC) concluded that the trial met the primary endpoint of rPFS in men with mCRPC who had not received treatment in the 1st-line setting including with new hormonal agents (NHAs) or chemotherapy.

The trial also showed a trend at this interim analysis towards improved overall survival (OS). However, the data are still immature and the trial will continue to assess OS as a key secondary endpoint. The safety and tolerability were consistent with the known profiles of each medicine.

Prostate cancer is the second-most common cancer in men and despite an increase in the number of available treatments for men with mCRPC, five-year survival remains low.1

Susan Galbraith, Executive Vice President, Oncology R&D, said: "Today, men with metastatic castration-resistant prostate cancer have limited options in the 1st-line setting, and sadly often the disease progresses after initial treatment with current standards of care. These exciting results demonstrate the potential for Lynparza with abiraterone to become a new 1st-line option for patients regardless of their biomarker status and reach a broad population of patients living with this aggressive disease. We look forward to discussing the results with global health authorities as soon as possible."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "We are encouraged by the PROpel results and the clinical benefit Lynparza in combination with abiraterone demonstrated versus abiraterone alone as a 1st-line treatment option for men with metastatic castration-resistant prostate cancer. Today’s results build on MSD and AstraZeneca’s commitment to bring Lynparza earlier in lines of treatment and to more patients with advanced prostate cancer."

The data will be presented at an upcoming medical meeting.

Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a significant mortality rate.2 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.3

In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.3 Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis.4

Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.4 Despite advances in treatment for men with mCRPC, five-year survival is low and extending survival remains a key treatment goal.4

PROpel
PROpel is a randomised, double-blind, multi-centre Phase III trial testing the efficacy, safety, and tolerability of Lynparza versus placebo when given in addition to abiraterone in men with mCRPC who had not received prior chemotherapy or NHAs in the 1st-line setting. Men in both treatment groups will also receive either prednisone or prednisolone twice daily. The primary endpoint is rPFS and secondary endpoints include OS and time to first subsequent anticancer therapy or death.

The trial enrolled men with or without HRR gene mutations. They may have previously been treated with docetaxel at a prior stage of disease. The trial excluded men with prior treatment with abiraterone. Treatment with any other NHA must have been stopped one year or longer prior to randomisation.

Men must have had a performance status of 0-1 as defined by the Eastern Cooperative Oncology Group (ECOG) criteria and be a candidate for abiraterone treatment with documented evidence of progressive disease.

Preclinical trials in prostate cancer report a combined anti-tumour effect when PARP inhibitors and NHAs are administered together. PARP-1 is involved in the co-regulation of the androgen-receptor (AR) pathway, potentially leading to cooperation between PARP inhibitors and NHAs in blocking AR signalling.5

PARP inhibition plus androgen deprivation could significantly reduce the growth of prostate cancer cells independent of HRR gene status. Other trials revealed that treatment with NHAs inhibit the transcription of some HRR genes, therefore, inducing HRR deficiency and increased sensitivity to PARP inhibitors via non-genetic mechanisms. 6

Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as NHAs).

Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in a number of countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer. It is approved in the US, the EU, Japan, China, and several other countries as 1st-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy.

It is also approved in the US, EU and Japan as a 1st-line maintenance treatment with bevacizumab for patients with HRD-positive advanced ovarian cancer (BRCAm and/or genomic instability).

Lynparza is approved in the US, Japan, and a number of other countries for germline BRCA-mutated, HER2-negative, metastatic breast cancer, previously treated with chemotherapy; in the EU, this includes locally advanced breast cancer.

It is also approved in the US, the EU, Japan and several other countries for the treatment of germline BRCAm metastatic pancreatic cancer. Lynparza is approved in the US for HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm and other HRR gene mutations) and in the EU and Japan for BRCAm metastatic castration-resistant prostate cancer.

Regulatory reviews are underway in several countries for ovarian, breast, pancreatic and prostate cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 40,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types.

Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

The AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types.

Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On September 24, 2021 Oasmia Pharmaceutical’s CEO, Dr Francois Martelet reported that it will present at the Naventus Life Science Summit at Grand Hotel in Stockholm on September 29, 2021 (Press release, Oasmia, SEP 24, 2021, View Source [SID1234590248]). The presentation starts at 10:50 CEST and will be live streamed via View Source

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The event is organized by Naventus Corporate Finance together with Setterwalls, Deloitte, FNCA, Nordnet and Nasdaq.

The presentation will be held in English and will also be available afterwards on Oasmia Pharmaceutical’s website www.oasmia.com

On September 23, 2021 Ayala Pharmaceuticals, Inc. (NASDAQ: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, reported the publication of two case studies of adult patients with desmoid tumors treated with AL101 in Current Oncology (Press release, Ayala Pharmaceuticals, SEP 23, 2021, View Source [SID1234594000]). This publication highlights the potential of a gamma secretase inhibitor for the treatment of desmoid tumors.

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The data included in the case study are based on earlier Phase 1 results and compassionate use of AL101 in desmoid tumors. Both patients showcased in these case studies, Case One and Case Two, presented with significant tumor burden and symptomatic and life-threatening disease due to disease bulk and location. Both patients achieved long-lasting partial responses (PR) with AL101 treatment with a maximal decrease in tumor size from baseline of 41% after approximately 1 year (55 weeks) of treatment in Case One, and a maximal decrease in tumor size from baseline of 60% after about 1.6 years (82 weeks) of treatment in Case Two. With continued monitoring, one patient was able to discontinue AL101 after 4.6 years of treatment, while maintaining a PR, and the other patient has maintained a PR at a reduced AL101 dose.

"Both of these patients’ case studies represent additional evidence to support the development of our gamma secretase inhibitor, AL102 for the treatment of desmoid tumors. The body of data conducted by BMS in patients with desmoid tumors implicating the role of gamma secretase inhibition furthers our hypothesis for treating desmoid tumors through AL102’s mechanism of action," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "Desmoid tumors continue to be an area of high unmet medical with a significant impact to patients’ quality of life, and we are pleased to have initiated our pivotal Phase 2/3 RINGISDE trial of AL102 to potentially address this gap in the existing treatment paradigm."

The pivotal Phase 2/3 RINGSIDE trial is designed to evaluate the efficacy, safety and tolerability of AL102 in adult and adolescent patients with desmoid tumors. Part 1 of the study is open label and will enroll up to 36 patients with progressive desmoid tumors in three study arms across three doses of AL102: 1.2 mg daily (QD), 2 mg twice weekly (QIW) and 4mg twice weekly (QIW) with initial follow up of safety, tolerability and tumor volume by MRI after 16 weeks in order to determine the optimal dose. At the end of part 1, all patients will be eligible to enroll into an open label extension study at the selected dose where long-term efficacy and safety will be monitored.

Part 2 of the study will start immediately after dose selection from part 1 and will be a double-blind placebo-controlled study enrolling up to 156 patients with progressive disease, randomized 2:1 between AL102 or placebo. The study’s primary endpoint will be progression free survival (PFS) with secondary endpoints including objective response rate (ORR), duration of response (DOR) and patient reported Quality of Life (QOL) measures.

About Desmoid Tumors

Desmoid tumors, also called aggressive fibromatosis or desmoid-type fibromatosis, are rare connective tissue tumors that typically arise in the upper and lower extremities, abdominal wall, head and neck area, mesenteric root and chest wall with the potential to arise in additional parts of the body. Desmoid tumors do not metastasize, but often aggressively infiltrate neurovascular structures and vital organs. People living with desmoid tumors are often limited in their daily life due to chronic pain, functional deficits, general decrease in their quality of life and organ dysfunction. Desmoid tumors have an annual incidence of approximately 1,700 patients in the United States and typically occur in patients between the ages of 15 and 60 years. They are most commonly diagnosed in young adults between 30-40 years of age and are more prevalent in females. Today, surgery is no longer regarded as the cornerstone treatment of desmoid tumors due to high rate of recurrence post-surgery and there are currently no FDA-approved systemic therapies for the treatment of unresectable, recurrent or progressive desmoid tumors.