On January Orphagen Pharmaceuticals, Inc., a biotech company pioneering the screening, discovery, and development of small molecule ligands that modulate orphan or unexplored members of the nuclear receptor family, reported that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD) for OR-449 for the treatment of pediatric adrenocortical carcinoma (ACC) (Press release, Orphagen, JAN 17, 2023, View Source [SID1234626280]).

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OR-449 is a selective, first-in-class, potent and orally bioavailable small molecule antagonist to steroidogenic factor-1 (SF-1 or NR5A1), an orphan nuclear receptor and transcription factor that is essential for the growth and development of the adrenal gland. Orphagen is developing OR-449 for both the adult and pediatric forms of ACC as well as other cancers known to express a high level of SF-1.

"We are gratified that OR-449 has received an RPDD from the FDA. We currently plan to file an Investigational New Drug (IND) application with the FDA later this year to support initiation of a Phase 1 clinical trial," said Orphagen CEO, Scott Thacher, Ph.D. "We speak to clinicians regularly who remind us of the urgent need for an improved therapy for patients with ACC, and this drives our commitment to the clinical development of OR-449, our first internal program to reach this stage."

About ACC and SF-1
ACC is a rare and aggressive cancer of the adrenal gland. Surgical removal of an affected adrenal gland is effective treatment if the tumor has not metastasized. Once an ACC tumor becomes metastatic, as it does for most patients, it is difficult to control and five-year survival in both adult and pediatric patients with metastatic disease is low, about 10-20%. The estimated annual incidence of ACC in the U.S. is 600 patients/year. In clinical practice, SF-1 is widely used as a marker for ACC, and it is recognized as a potential therapeutic target for both adult and pediatric ACC. SF-1 is commonly amplified at the gene level in pediatric ACC, and SF-1 is recognized as a cell lineage marker in the FDA’s Pediatric Cancer Target List.

Rare Pediatric Disease Designation
A rare pediatric disease is defined by the Federal Food, Drug, and Cosmetic Act to include a serious or life-threatening disease, which primarily affects individuals aged from birth to 18 years and affects fewer than 200,000 people in the U.S. To address the challenges that drug companies face when developing treatments for these unique patient populations, Congress reauthorized the Creating Hope Act. Since first enacted by Congress in 2012, the Creating Hope Act has been extended multiple times, most recently on December 27, 2020. Under this Act, companies are eligible to receive a Priority Review Voucher (PRV) following approval of a product with an RPDD if the marketing application receives FDA approval by September 30, 2026, under current legislation, or at a later date if the Act is extended by Congress. If issued, a sponsor may redeem a PRV for priority review of a subsequent marketing application for a different product candidate, or the PRV can be sold or transferred to another sponsor.

On January 17,2023 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of therapeutics to treat multiple types of cancers, immune disorders, and viral diseases – including COVID-19, the disease caused by the SARS-CoV-2 virus – reported it has entered into an external sponsored collaborative clinical research agreement with Erasmus MC and AstraZeneca (Press release, AIM ImmunoTech, JAN 17, 2023, View Source [SID1234626277]).

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Under the agreement, Erasmus MC is planning to perform an investigator-initiated clinical study, entitled "Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy effect. DURIPANC Study," in which it will use both Study Drugs provided by AstraZeneca and AIM ImmunoTech.

"We have been diligently working to advance the development of Ampligen as a synergistic combination therapy with checkpoint inhibitors based on the promising data demonstrated to date. In the previously conducted human clinical studies, Ampligen has shown synergistic potential with PD-1 checkpoint blockade therapeutics. We are thrilled to take this important step forward in clinical development in collaboration with AstraZeneca and its PDL-1 therapy, durvalumab, and further unlock the potential of Ampligen for the treatment of pancreatic cancer where there remains significant unmet need," commented Thomas K. Equels, MS JD, Chief Executive Officer of AIM.

Prof. Casper H.J. van Eijck, MD, PhD, Pancreato-biliary Surgeon at Erasmus MC, added, "PD-L1 expression levels in the malignant tumors of pancreatic cancer patients correlates to poor prognosis. While immune checkpoint inhibitors targeting PD1/PDL1 have shown promise in other solid tumors, they have shown limited efficacy thus far in ductal cancer of the pancreas. This may be in part due to limited CD8+ T-cell maturation necessary for the immune system to combat the cancer. We are excited about the promise of combining Ampligen with durvalumab as previous data has shown that Ampligen can prime dendritic cells and enhance the maturation of T-cells essentially activating the immune system through its activation of TLR3 while durvalumab will bind PD-L1 and ‘uncloak’ the tumor cells in the tumor microenvironment allowing them to be recognized and attacked by the immune system. We believe this one-two punch of TLR-3 stimulation and PD-L1 blockade could lead to synergistic anti-tumor immunity in patients and extend overall and progression free survival in patients with metastatic pancreatic cancer."

Ampligen is AIM’s dsRNA drug currently being developed for globally important cancers. Ampligen has shown therapeutic synergy with checkpoint inhibitors, including increasing survival rates and efficacy, in the treatment of animal tumors when used in combination with checkpoint blockade therapies. The first detection of Ampligen’s synergistic potential with checkpoint blockade therapeutics was witnessed in pre-clinical mouse models of melanoma and pancreatic cancers. Additionally, there is published data from two recent clinical studies – in triple-negative breast cancer and advanced recurrent ovarian cancer – that further support Ampligen’s potential to enhance checkpoint blockade therapy efficacy.

About AIM ImmunoTech Inc.

On January 1, 2023 Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported a placement of KZA shares, to institutional and sophisticated investors in Australia, at a price of A$0.11 per share (Press release, Kazia Therapeutics, JAN 17, 2023, View Source [SID1234626276]). The placement will raise A$4.5 million (exclusive of costs).

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Placement

The Placement to professional and sophisticated investors consists of an:

A$2,792,572 unconditional institutional placement of 25,387,018 New Shares, representing approximately 16% of the total shares of Kazia on issue prior to the issue of the New Shares; and

A$1,707,428 institutional placement of 15,522,075 New Shares, conditional on Kazia shareholder approval for the purposes of ASX Listing Rule 7.1.

The price of both the Unconditional Placement and the Conditional Placement will be A$0.11 which represents a 13% premium to the 15-day volume-weighted average price (VWAP) on the Australian Securities Exchange (ASX) up to and including 11 January 2023 of A$0.097.

New Shares to be issued under the Unconditional Placement will be issued without shareholder approval under the Company’s existing placement capacity under ASX Listing Rules 7.1. Settlement and issuance of shares is expected to occur on or around January 16, 2023, with quotation expected on January 17, 2023 in Australia. The New Shares will rank equally with the Company’s existing shares on issue.

An Extraordinary General Meeting (EGM) is expected to be held on 24 February 2023 to seek approval for the issuance of New Shares under the Conditional Placement. Kazia will provide eligible shareholders with a notice of meeting and explanatory materials over the coming days.

The Placement was not underwritten.

Funding will be used to drive Kazia’s clinical program toward several critical inflection points, including the final data read out on the paxalisib GBM AGILE study.

On January 17, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, reported that the Company’s management team will participate in a fireside chat on Thursday, January 19, 2023 at 10:30 AM EST at the 3rd Annual B. Riley Securities Oncology Conference (Press release, Actinium Pharmaceuticals, JAN 17, 2023, View Source [SID1234626275]). The webcast of the presentation will be accessible on the event’s website at View Source and on the investor relations page of Actinium’s website View Source A replay of the presentation will be available on the day of the fireside chat through the same links.

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B. Riley Securities 3rd Annual Oncology Conference

B. Riley Securities 3rd Annual Oncology Conference, January 18-19, will feature over 30 SMiD cap healthcare companies focused on the development and commercialization of new medicines and key enabling technologies, cutting across multiple next-generation therapeutic modalities. The conference will feature KOL panel discussions with academic and industry leaders at the forefront of translational and clinical research underway with novel immunotherapy, cell therapy, and targeted oncology approaches, as well as imaging and radiation oncology initiatives, aimed at driving meaningful improvements to current standard of care for cancer patients.

On January 17, 2023 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, and Flame Biosciences, Inc., a privately-held biotechnology company, reported that the companies have entered into a definitive merger agreement pursuant to which Leap has acquired Flame and its assets, including FL-301, its clinical stage anti-Claudin18.2 monoclonal antibody, FL-302, its preclinical anti-Claudin18.2/CD137 bispecific monoclonal antibody, FL-501, its preclinical anti-GDF15 monoclonal antibody, and net cash of approximately $50 million as of December 31, 2022 (Press release, Leap Therapeutics, JAN 17, 2023, View Source [SID1234626274]).

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The combined company will continue to trade on Nasdaq under the ticker symbol "LPTX," will be led by Leap’s existing management team, and will also remain focused on advancing DKN-01, Leap’s anti-DKK1 monoclonal antibody, in Phase 2 clinical trials in gastric cancer, endometrial cancer, and colorectal cancer patients. The total cash balance of the combined company as of December 31, 2022 was approximately $115 million, expected to be sufficient to fund Leap’s planned operating expenses and development plans for DKN-01, FL-301, and the preclinical programs to mid-2025.

"This is a transformative transaction for Leap. Acquiring FL-301 is a perfect fit with our vision of developing novel biomarker-targeted therapies for cancer patients, that is represented by our DKN-01 program. We believe that DKK1 and Claudin18.2 will become important patient selection biomarkers in gastric cancer, alongside HER-2 and PD-L1 expression, with the potential for delivering personalized medicines to patients who currently have poor survival outcomes," said Douglas E. Onsi, President & CEO of Leap. "The additional pipeline strength is further enhanced by additional financial strength. With the combined company resources, Leap will focus on executing on the randomized controlled trial for DKN-01 in combination with BeiGene’s tislelizumab and chemotherapy in first-line gastric cancer patients, the new study of DKN-01 in colorectal cancer patients, and the investigator-sponsored trial of DKN-01 in combination with Merck’s pembrolizumab in endometrial cancer patients."

"Flame conducted an extensive strategic process. It was clear that the Leap development team, with its expertise in developing DKN-01, was the ideal partner for FL-301, our preclinical assets, and the Flame shareholders," said Patricia Martin, the Co-Chief Executive Officer of Flame.

"We share Leap’s commitment to developing novel, biomarker-targeted therapies in cancers where there is a significant unmet need and look forward to joining them to bring DKN-01 and FL-301 to patients around the world," said Christian Richard, Head of Public Research of Samsara BioCapital.

Transaction Details

In the merger, Leap will issue approximately 19,794,373 shares of its common stock and approximately 136,833 shares of a newly designated Series X non-voting convertible preferred stock to Flame stockholders. Upon approval by the stockholders of Leap, each share of the Series X non-voting convertible preferred stock will be automatically converted into 1,000 shares of common stock. Flame’s institutional shareholders include Rock Springs Capital, funds and accounts advised by T. Rowe Price Associates, Inc., Janus Henderson Investors, Samsara BioCapital, Adage Capital Management LP, Cormorant Asset Management LP, Surveyor Capital (a Citadel company), Terra Magnum Capital Partners, Logos Capital, and Acuta Capital Partners. In addition, Leap will pay the Flame shareholders 80% of the after-tax net proceeds, if any, from certain post-merger transactions to out-license or sell FL-101 or FL-103, Flame’s anti-IL-1b antibodies.

Leap plans to hold a special meeting of stockholders to approve the conversion of the Series X non-voting convertible preferred stock into shares of common stock and related matters. The number of shares of Leap common stock issuable upon conversion of the Series X non-voting convertible preferred stock are subject to adjustment in the event of any corporate transactions or reverse stock split that may be effectuated by Leap. HealthCare Ventures, which holds 6,763,210 shares or 6.83% of Leap’s outstanding common stock, has signed a support agreement to vote in favor of the proposals to be presented at the shareholder meeting. Assuming the approval by the Leap stockholders, on an as-converted basis, the Flame shareholders will in the aggregate own 58% of the outstanding shares including pre-funded warrants of Leap, and 47.4% on a fully-diluted basis assuming the exercise of all outstanding warrants, options and restricted stock units exercisable for Leap common stock and shares eligible for grant under Leap’s equity incentive plans.

The securities sold in the merger have not been registered under the Securities Act of 1933, as amended ("Securities Act"), or any state or other applicable jurisdiction’s securities laws, and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws. Leap has agreed to file a registration statement with the U.S. Securities and Exchange Commission (the "SEC") to register the resale by the Flame stockholders of the shares of Leap common stock to be issued in connection with the merger.

Raymond James acted as exclusive financial advisor to Leap on the transaction.

Management and Organization

Effective as of the closing of the transactions, the Leap leadership team will continue to be responsible for all executive positions of the combined company. Leap has added two members nominated by Flame to its existing eight person Board of Directors: Patricia Martin and Christian Richard.

About DKN-01

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways and has an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immune suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells. The U.S. Food and Drug Administration has granted DKN-01 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.

About FL-301

FL-301 is a fully human monoclonal antibody that binds to and blocks Claudin18.2. Claudin18.2 regulates barrier properties and contributes to cell-to-cell adhesion. Expression of Claudin18.2 is very limited in normal tissue, as it is typically buried in the tight junction complex of gastric mucosal cells. In the development of cancer, however, cells lose their polarity and structure. As a result, Claudin18.2 may be exposed and accessible as a target for cancer therapy and is highly expressed on gastric cancer and pancreatic cancer cells. The U.S. Food and Drug Administration has granted FL-301 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and for the treatment of pancreatic cancer. FL-301 is being developed through an exclusive license from NovaRock Biotherapeutics for territories excluding China and is currently in a Phase 1 clinical trial in cancer patients in China.

Conference Call Information

Leap’s management team will host a conference call today at 9:00 a.m. Eastern Time to discuss the transaction. The live presentation of the conference call can be accessed by registering here. A replay of the event will be available for a limited time and may be access on the Investors page of Leap’s website at View Source