On July 1, 2024 AstraZeneca reported its Imfinzi (durvalumab) and Lynparza (olaparib) have been recommended for approval in the European Union (EU) as treatment for certain patients with primary advanced or recurrent endometrial cancer (Press release, AstraZeneca, JUL 1, 2024, View Source [SID1234644635]). Imfinzi plus chemotherapy as 1st-line treatment followed by Lynparza and Imfinzi has been recommended for patients with mismatch repair proficient (pMMR) disease. Imfinzi plus chemotherapy followed by Imfinzi alone has been recommended for patients with mismatch repair deficient (dMMR) disease.

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The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on a prespecified exploratory subgroup analysis by mismatch repair (MMR) status from the DUO-E Phase III trial, which was published in the Journal of Clinical Oncology in October 2023.

This analysis showed a reduction in the risk of disease progression or death for pMMR patients in the Lynparza and Imfinzi arm by 43% (median 15.0 months versus 9.7 months, hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.44-0.73) versus the control arm.1 Results for dMMR patients showed a reduction in the risk of disease progression or death in the Imfinzi arm by 58% (median not reached versus 7.0 months, HR 0.42; 95% CI 0.22-0.80) versus the control arm.1

In Europe, endometrial cancer is the fourth most common cancer in women, with nearly 125,000 diagnoses and more than 30,000 deaths in 2022.2,3 Patients diagnosed at an early stage of disease have a five-year survival rate of approximately 80-90%, but that falls to less than 20% for people with advanced disease.4,5 There is a significant need for new treatment options, especially for the 70-80% of patients with pMMR disease.5,6 This recommendation underscores the importance of MMR testing at point of diagnosis, which is well established and widely available.7,8

Els Van Nieuwenhuysen, Gynaecological Oncologist at the UZ Leuven, Belgium and trial investigator, said: "Patients with advanced or recurrent endometrial cancer currently have a very poor prognosis, especially those with mismatch repair proficient disease. This recommendation underscores the significant benefit shown with durvalumab as well as with the olaparib and durvalumab combination for patients with both mismatch repair deficient and mismatch repair proficient status. This marks an important step toward improving outcomes for these patients in Europe."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "Today’s recommendation for approval in the EU recognises the potential of the Lynparza and Imfinzi combination to provide clinical benefit for patients with endometrial cancer, especially for those with mismatch repair proficient disease who have few available treatments today. If approved, patients in Europe will have a new option for combination treatment that brings the additional benefit of PARP inhibition to immunotherapy."

The safety profiles of both experimental regimens were manageable, well-tolerated and broadly consistent with the known profiles of the individual agents.1,9,10

Regulatory submissions for Imfinzi and Lynparza are currently under review in Japan and several other countries based on the DUO-E trial. Imfinzi plus chemotherapy was recently approved for dMMR patients with primary advanced or recurrent endometrial cancer in the US.11

Notes

Endometrial cancer
Endometrial cancer is a highly heterogeneous disease that originates in the tissue lining of the uterus and is most common in women who have already been through menopause, with the average age at diagnosis being over 60 years old.12-15

The majority of patients with endometrial cancer are diagnosed at an early stage of disease, where the cancer is confined to the uterus.16 They are typically treated with surgery and/or radiation, and the five-year survival rate is high (approximately 80-90%).17 Patients with advanced disease (Stage III-IV) usually have a much poorer prognosis, with the five-year survival rate falling to less than 20%.4 Immunotherapy combined with chemotherapy is emerging as a new standard of care for advanced endometrial cancer, particularly for patients with dMMR disease, who make up approximately 20-30% of all patients.11,17-20 There remains a high unmet need for treatments for the remaining 70-80% of endometrial cancer patients with pMMR disease.5,6

DUO-E
The DUO-E trial (GOG 3041/ENGOT-EN10) is a three-arm, randomised, double-blind, placebo-controlled, multicentre Phase III trial of 1st-line Imfinzi (durvalumab) plus platinum-based chemotherapy (carboplatin and paclitaxel) followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) as maintenance therapy versus platinum-based chemotherapy alone as a treatment for patients with newly diagnosed advanced or recurrent endometrial cancer.

The DUO-E trial randomised 699 patients with newly diagnosed advanced or recurrent epithelial endometrial carcinoma to receive either Imfinzi (1120mg) or placebo, given every three weeks in addition to standard-of-care platinum-based chemotherapy. After 4-6 cycles of chemotherapy, patients (whose disease had not progressed) then received either Imfinzi (1500mg) or placebo every four weeks as maintenance, plus 300mg Lynparza (300mg BID [2x150mg tablets, twice a day]) or placebo until disease progression.

The dual primary endpoint was progression-free survival (PFS) of each treatment arm versus standard of care. Key secondary endpoints included overall survival (OS), safety and tolerability. The trial continues to assess OS for both Imfinzi monotherapy and Imfinzi plus Lynparza as maintenance therapy in the overall trial population. Mismatch repair (MMR) status, recurrence status and geographic location were stratification factors. The trial was sponsored independently by AstraZeneca and conducted in 253 study locations across 22 countries including the US, Europe, South America and Asia.

For more information about the trial, please visit ClinicalTrials.gov.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage small cell lung cancer (SCLC) and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC.

In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal cancers and other solid tumours.

Lynparza
Lynparza 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-related (HRR) genes, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as new hormonal agents [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 may also help enhance immunogenicity and increase the impact of anti-tumour immune responses.

Lynparza is currently approved in a number of countries across multiple tumour types, including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for germline BRCA mutation (gBRCAm), HER2-negative metastatic breast cancer (in the EU and Japan, this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan, this includes all BRCAm HER2-negative high-risk early breast cancer); for gBRCAm metastatic pancreatic cancer; in combination with abiraterone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) when chemotherapy is not clinically indicated (EU only) and for BRCAm mCRPC (US and Japan); and as monotherapy for HRR gene-mutated mCRPC in patients who have progressed on prior NHA treatment (BRCAm only in the EU and Japan). In China, Lynparza is approved for the treatment of BRCA-mutated mCRPC as well as 1st-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer.

Lynparza is being jointly developed and commercialised by AstraZeneca and MSD, both as a monotherapy and in combination with other potential medicines. Independently, the companies are developing and will commercialise Lynparza in combination with their respective PD-L1 and PD-1 medicines, Imfinzi (durvalumab) and Keytruda (pembrolizumab). Lynparza has been used to treat approximately 140,000 patients worldwide. Lynparza has a broad clinical trial development programme, 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.

On July 1, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer and rare diseases, reported that the Company’s President and Chief Executive Officer, Kristin Yarema, Ph.D., will participate in a virtual fireside chat at the Stifel 2024 Virtual Cell Therapy Forum on Tuesday, July 9, 2024 at 7:55am PT | 10:55am ET (Press release, Poseida Therapeutics, JUL 1, 2024, View Source [SID1234644634]).

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A live webcast of the fireside chat will be available on the Investors & Media Section of Poseida’s website, www.poseida.com. A replay of the webcast will be available for approximately 90 days following the presentation.

On July 01, 2024 DiaMedica Therapeutics Inc., a clinical-stage biopharmaceutical company focused on developing novel treatments for severe ischemic disease, reported the closing of its previously announced $11.8 million private placement to accredited investors (Press release, DiaMedica, JUL 1, 2024, View Source [SID1234644633]). The Company sold approximately 4.7 million common shares at a purchase price of $2.50 per share, a premium of approximately 10% above the Company’s per share closing price on Tuesday June 25, 2024. After deducting estimated offering expenses, the Company received net proceeds of approximately $11.7 million.

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The Company reported cash, cash equivalents and short-term investments of $46.5 million as of March 31, 2024. On a pro forma basis, including the estimated $11.7 million in net proceeds from the private placement, the Company’s cash, cash equivalents and short-term investments would have been $58.2 million as of such date.

The securities sold in the private placement have not been registered under the U.S. Securities Act of 1933, as amended, or any state or other applicable jurisdiction’s securities laws, and may not be offered or sold in the United States absent such registration or an applicable exemption therefrom. The Company has agreed to file a registration statement with the U.S. Securities and Exchange Commission registering the resale of the common shares issued in the private placement.

This release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of the Company’s securities in any state or other 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 other jurisdiction.

Required Canadian Early Warning Reporting

Upon closing of the private placement, Thomas von Koch (the "von Koch"), c/o EQT Partners AB, Box 16509, 103 27 Stockholm, Sweden, will acquire indirect ownership, through TomEnterprise Private AB, of an aggregate of 1,200,000 common shares (the "von Koch Shares") of DiaMedica (the "von Koch Acquisition"). The Company’s head office is located at 301 Carlson Parkway, Suite 210, Minneapolis, Minnesota, 55305, U.S.A. Immediately prior to the completion of the von Koch Acquisition, von Koch had ownership of, and exercised control and direction over, an aggregate of 4,326,435 common shares of the Company representing approximately 11.4% of the issued and outstanding common shares of the Issuer on a non-diluted basis. Immediately following the completion of the von Koch Acquisition, von Koch will have ownership of, and exercise control and direction over, an aggregate of 5,526,435 common shares of the Company representing approximately 12.9% of the issued and outstanding common shares of the Company on a non-diluted basis. von Koch will pay aggregate cash consideration of US$3,000,000 (approximately C$4,098,000) for the von Koch Shares at a price of US$2.50 per common share (approximately C$3.41). The von Koch Shares are being acquired for investment purposes. von Koch may, from time to time, take such actions in respect of his holdings in securities of the Company as he may deem appropriate in light of the circumstances then existing, including the purchase of additional common shares or other securities of the Company or the disposition of all or a portion of his security holdings in the Company, subject in each case to applicable securities laws and the terms of such securities.

Upon closing of the private placement, Trill AB ("Trill"), Sveavägen 17, 18th Floor, SE-111 57, Stockholm, Sweden, acquired ownership of an aggregate of 1,200,000 common shares (the "Trill Shares") of the Company (the "Trill Acquisition"). Immediately prior to the completion of the Trill Acquisition, Trill had ownership of, and exercised control and direction over, an aggregate of 4,021,608 common shares of the Company representing approximately 10.6% of the issued and outstanding common shares of the Company on a non-diluted basis. Immediately following the completion of the Trill Acquisition, Trill will have ownership of, and exercise control and direction over, an aggregate of 5,221,608 common shares of the Company representing approximately 12.2% of the issued and outstanding common shares of the Company on a non-diluted basis. Trill will pay aggregate cash consideration of US$3,000,000 (approximately C$4,098,000) for the 1,200,000 Trill Shares at a price of US$2.50 per common share (approximately C$3.41). The Trill Shares are being acquired for investment purposes. Trill may, from time to time, take such actions in respect of its holdings in securities of the Company as it may deem appropriate in light of the circumstances then existing, including the purchase of additional common shares or other securities of the Company or the disposition of all or a portion of its security holdings in the Company, subject in each case to applicable securities laws and the terms of such securities.

Pursuant to National Instrument 62-103 – The Early Warning System and Related Take-Over Bid and Insider Reporting Issues, following the closing of the private placement, each of von Koch and Trill will file an early warning report in respect of the von Koch Acquisition and Trill Acquisition, respectively, with the applicable Canadian securities regulators, copies of which will be available under the Company’s profile at www.sedar.com. Following closing of the private placement, a copy of the early warning report relating to the von Koch Acquisition can be obtained by contacting von Koch at +46706034564, Per Colleen, CEO TomEnterprise Private AB. A copy of the early warning report relating to the Trill Acquisition can be obtained by contacting Trill at Sveavägen 17, 18th Floor, SE-111 57, Stockholm, Sweden.

The Canadian dollar values referred to above were determined using the Bank of Canada daily exchange rate on June 25, 2024.

About DM199 (rinvecalinase alfa)

DM199 is a recombinant (synthetic) form of human tissue kallikrein-1 (rhKLK1) in clinical development for acute ischemic stroke (AIS) and preeclampsia. KLK1 is a serine protease enzyme that plays an important role in the regulation of diverse physiological processes via a molecular mechanism that increases production of nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. In the case of AIS, DM199 is intended to enhance blood flow and boost neuronal survival in the ischemic penumbra by dilating arterioles surrounding the site of the vascular occlusion and inhibition of apoptosis (neuronal cell death) while also facilitating neuronal remodeling through the promotion of angiogenesis. In preeclampsia, DM199 is intended to lower blood pressure, enhance endothelial health and improve perfusion to maternal organs and the placenta.

On July 1, 2024 Aptevo Therapeutics Inc., a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported the closing of its previously announced offering of (i) 5,339,806 shares of its common stock or pre-funded warrants in lieu thereof and (ii) warrants to purchase up to an aggregate of 10,679,612 shares of its common stock (the "Common Warrants") at a purchase price of $0.515 per share and associated Common Warrant in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Aptevo Therapeutics, JUL 1, 2024, View Source [SID1234644632]). Each share of common stock is being offered together with two Common Warrants, each to purchase one share of common stock. The Common Warrants have an exercise price of $0.515 per share, are exercisable upon stockholder approval, and will expire five years following the date stockholder approval.

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Roth Capital Partners acted as placement agent of the offering, with Dawson James Securities, Inc. acted as co-agent. Gross proceeds, before deducting placement agent fees and commissions and offering expenses, were approximately $2.75 million. The company intends to use the net proceeds from the offering for the continued clinical development of its product candidates, working capital, and other general corporate purposes.

The securities described above were offered pursuant to a registration statement on Form S-1 (File No. 333-280226), as amended, that was declared effective by the U.S. Securities and Exchange Commission ("SEC"), on June 28, 2024. The offering was made solely by means of a prospectus. Copies of the accompanying prospectus relating to and describing the terms of the offering may be obtained at the SEC’s website at www.sec.gov or by contacting Roth Capital Partners, LLC, 888 San Clemente Drive, Suite 400, Newport Beach, CA 92660 or by email at [email protected]. This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of these securities in any state or other 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 other jurisdiction. All offers were made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement.

The Company also amended certain existing warrants that were previously issued in (i) August 2023 to purchase up to 41,239 shares of the Company’s common stock and have exercise price of $27.28 per share, (ii) November 2023 to purchase up to 610,334 shares of the Company’s common stock and have exercise price of $10.252 per share, and (iii) April 2024 to purchase up to 6,666,668 shares of the Company’s common stock and have exercise price of $1.35 per share, whereas effective upon the closing of the offering, such existing warrants have a reduced exercise price of $0.515 per share and shall become exercisable upon stockholder approval.

On July 1, 2024 Vivos Inc. reported the company filed the application for an Investigational Device Exemption ("IDE") (Press release, Vivos, JUL 1, 2024, View Source [SID1234644629]).

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The filing was an amendment, addressing the FDA comments to our previous application (Q211938/S001). Today’s IDE submission marks our first filing with the FDA following the grant of the FDA Breakthrough Device Designation for the Radiogel Precision Radionuclide Therapy. We are appreciative of the improved communication with the FDA since receiving the breakthrough designation. Our IDE filing contained reports on two complex studies, RadioGel genotoxicity and the retention of RadioGel at the injection site in VX2 tumors in rabbits. This current IDE submission addressed the 63 FDA comments received in previous FDA correspondences. In some cases, we repeated underlying testing to strengthen our answers with current data. Dr. Korenko stated, "we are mindful that most of the twelve FDA reviewers have joined in the past two years and we anticipate they will have some comments after reviewing the extensive material in our filing, which we are prepared to address promptly."

In closing Dr. Korenko stated, "We are eager to secure the FDA’s IDE approval so that we can submit our plan to the Mayo Clinic’s Internal Review Board (IRB) for clearance to initiate the first in human clinical trials. This is an exciting time for Vivos and we are committed to bringing a new treatment option to patients in the fight against challenging cancer types. Initially our collaboration with Mayo will be targeting solid metastatic tumors in lymph nodes associated with papillary thyroid cancer.

Dr. Michael Korenko

Vivos Inc.

Michael K. Korenko, Sc.D.

President & CEO

Email: [email protected]

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