On June 5, 2023 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition" or the "Company"), a multi-national epigenetics company, reported that it has commenced an underwritten public offering of shares of its common stock (Press release, VolitionRX, MAY 31, 2023, View Source [SID1234632481]). In addition, Volition intends to grant the underwriters a 30-day option to purchase up to an additional 15% of the number of shares of common stock offered in the offering at the public offering price, less underwriting discounts and commissions. All of the shares of common stock in the offering are being offered by Volition. The final terms of the proposed offering will depend on market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

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Volition intends to use the net proceeds from the offering for research and continued product development, clinical studies, product commercialization, working capital and other general corporate purposes, including potential strategic acquisitions.

Freedom Capital Markets is acting as the book-running manager of the offering and Bancroft Capital is acting as co-manager.

The securities are being offered by Volition pursuant to a "shelf" registration statement on Form S-3 (File No. 333-259783) previously filed with the Securities and Exchange Commission (the "SEC") on September 24, 2021, as amended on November 4, 2021, and declared effective by the SEC on November 8, 2021. The offering is being made only by means of a prospectus supplement and an accompanying base prospectus, as may be further supplemented by any free writing prospectus and/or pricing supplement that the Company may file with the SEC. A preliminary prospectus supplement and an accompanying base prospectus describing the terms of the proposed offering have been filed with the SEC and are available on the SEC’s website at www.sec.gov. The final prospectus supplement relating to the offering will be filed with the SEC and will also be available on the SEC’s website. Copies of the preliminary prospectus supplement, the final prospectus supplement and the accompanying base prospectus relating to the offering can also be obtained, when available, in writing from Freedom Capital Markets, 40 Wall Street, 58th Floor, New York, NY 10005, or via email at [email protected] and via telephone at (800) 786-1469.

This press release shall 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 other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On May 31, 2023, Avalo Therapeutics, Inc. (the "Company") reported to have entered into an exchange agreement (the "Exchange Agreement") with entities affiliated with Venrock Healthcare Capital Partners (the "Exchanging Stockholders"), pursuant to which the Company exchanged an aggregate of 1,300,000 shares of the Company’s common stock, par value $0.001 per share (the "Common Stock"), owned by the Exchanging Stockholders for pre-funded warrants (the "Exchange Warrants") to purchase an aggregate of 1,300,000 shares of common stock (subject to adjustment in the event of stock splits, recapitalizations and other similar events affecting common stock), with an exercise price of $0.001 per share (Filing, 8-K, Avalo Therapeutics, MAY 31, 2023, View Source [SID1234632388]). The Exchange Warrants will be exercisable at any time, except that the Exchange Warrants will not be exercisable by the Exchanging Stockholders if, upon giving effect or immediately prior thereto, the Exchanging Stockholders would beneficially own more than 9.99% of the total number of issued and outstanding Common Stock, which percentage may change at the holders’ election to any other number less than or equal to 19.99% upon 61 days’ notice to the Company. The holders of the Exchange Warrants will not have the right to vote on any matter except to the extent required by Delaware law.

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The descriptions of the Exchange Agreement and the Exchange Warrants are not complete and are qualified in their entirety by reference to the Exchange Agreement and the form of Exchange Warrant, which are filed as Exhibit 10.1 and Exhibit 4.1, respectively, to this Current Report on Form 8-K and incorporated herein by reference. The representations, warranties and covenants made by the Company in the Exchange Agreement and the Exchange Warrants were made solely for the benefit of the parties to the Exchange Agreement and the Exchange Warrants, as applicable, including, in some cases, for the purpose of allocating risk among the parties thereto, and should not be deemed to be a representation, warranty or covenant to investors. Moreover, such representations, warranties or covenants were made as of an earlier date. Accordingly, such representations, warranties and covenants should not be relied on as accurately representing the current state of our affairs.

On May 31, 2023 HighField Biopharmaceuticals (HighField Bio), a clinical stage immuno-oncology company using immunoliposomes to treat cancer, reported the publication of an abstract including preliminary data from a Phase 1a clinical trial of HF1K16 in refractory metastatic cancer patients (Press release, HighField Biopharmaceuticals, MAY 31, 2023, View Source [SID1234632317]). It was published online at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. HF1K16 is a drug encapsulated immune modulating liposome containing all-trans retinoic acid. The ASCO (Free ASCO Whitepaper) meeting is June 2 – 6, 2023, at the McCormick Place, Chicago, IL.

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The HighField Bio abstract is titled "Modulating MDSCs by HF1K16: a monotherapy Phase 1a study examining safety and preliminary efficacy in refractory and metastatic cancer patients."

"We are excited about the preliminary data," said Yuhong Xu, CEO of HighField Bio. "The data show HF1K16 is well tolerated and patients have experienced significant progression-free survival." The abstract also reports that of the 11 patients treated, three who suffer from recurrent and refractory glioma continued to experience progression-free survival. One patient has been on treatment for 348 days. The other two are 94 days and 52 days with progression-free survival from the start of treatment.

Dr. Xu noted, "Four patients reached stable disease diagnosis based on RECIST 1.1 criteria. One patient experienced a reduction in size of the main brain lesion from 70mm to 23.7mm."

HF1K16 is a unique liposome construct of ATRA, a small molecule metabolite of vitamin A, administered by infusion, and travels through the blood stream and infiltrates the tumor microenvironment. ATRA is released and initiates the maturation of Myeloid-Derived Suppressor Cells (MDSCs).

MDSCs are immature myeloid cells which have not differentiated. ATRA promotes the maturation and differentiation of MDSCs into functional cells, such as dendritic cells, which then summon T cells to attack the cancer.

The preliminary data reported at ASCO (Free ASCO Whitepaper) is from an ongoing Phase 1a trial in China with patients suffering from a variety of refractory metastatic cancers. Based on the positive findings related to glioma, HighField Bio expects to begin a Phase 1b/2 trial in China for patients with refractory glioma in the next few weeks.

On May 31, 2023 Gamida Cell Ltd. (Nasdaq: GMDA), a cell therapy pioneer working to turn cells into powerful therapeutics, reported that an oral presentation highlighting Gamida Cell’s investigational natural killer (NK) cell therapy candidate GDA-201 will be shared at the International Society for Cell and Gene Therapy (ISCT) 2023 Annual Meeting (Press release, Gamida Cell, MAY 31, 2023, View Source [SID1234632316]). The meeting takes place May 31-June 3 in Paris, France.

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Additionally, a poster will be presented with data from Gamida Cell’s pre-clinical NK cell therapy candidate GDA-501, an engineered intrinsic NK cell with a CAR modification targeting the HER2 protein.

"The data being presented at ISCT add to the body of evidence demonstrating the power of our nicotinamide (NAM) technology to enhance and expand cells," said Ronit Simantov, M.D., Chief Medical and Scientific Officer of Gamida Cell. "The unique, active phenotype of NAM-NK cells and the high levels of potency and cytotoxicity observed support the strong potential of GDA-201 as a cell therapy for cancer."

Additional details about the presentations are as follows:

Title: GDA-201: Phenotypic and Functional Characterization of Cryopreserved Nicotinamide-Expanded Allogeneic Natural Killer Cells Demonstrate an Activated and Non-exhausted Phenotype
Abstract Number: 36
Presentation Date: June 2, 9:15-10:15 am CET
Presenting Author: Yona Geffen, Ph.D.; Vice President of R&D at Gamida Cell

Highlights: This study investigated the phenotype and function of GDA-201, NK cells expanded using Gamida Cell’s proprietary NAM technology. NAM-NK demonstrated increased expression of lymphoid homing marker CD62L and decreased levels of lineage exhaustion markers CD57 and CD161 compared with NK cells expanded in the absence of NAM. Batch-to-batch variability of 18 batches of cryopreserved formulation of GDA-201 from 18 donors demonstrated an overall variability of ≤25% in critical parameters including viability, phenotyping and cytotoxicity.
Title: GDA-501 HER2 Chimeric Antigen Receptor Natural Killer Cells: Dual Cytotoxicity in Solid Tumors Mediated via HER2 and TRAIL
Abstract Number: 1225
Presentation Date: June 1, 6-7:30 pm CET
Presenting Author: Julia Rifman, Ph.D.; Senior Project Manager at Gamida Cell

Highlights: GDA-501, an expanded, enhanced and engineered NAM HER2-CAR NK cell, showed high levels of TNF-related apoptosis-inducing ligand (TRAIL) expression, suggesting possible meditation of target cell apoptosis. Compared with non-engineered NK cells cultured with NAM, GDA-501 cells displayed increased cytotoxicity against HER2+ tumor cells. When TRAIL was neutralized on GDA-501, a decrease in cytotoxicity was observed. These data suggest that the cytotoxic effect of GDA-501 may be mediated by dual mechanisms: HER2 binding by the HER2-CAR and apoptosis mediated by TRAIL.
Note: Gamida Cell announced it would discontinue the development of GDA-501 in March 2023.
About GDA-201

GDA-201 is an intrinsic NK cell therapy candidate being investigated for the treatment of hematologic malignancies. Preclinical studies have shown that GDA-201 may address key limitations of cultured NK cells by increasing cytotoxicity and in vivo retention as well as proliferation in the bone marrow and lymphoid organs. Furthermore, these data suggest GDA-201 may improve antibody-dependent cellular cytotoxicity (ADCC) and tumor targeting of NK cells. A multicenter Phase 1/2 study of GDA-201 for the treatment of non-Hodgkin lymphoma is ongoing (NCT05296525).

GDA-201 is an investigational cell therapy candidate, and its safety and efficacy have not been established by the FDA or any other health authority.

On May 31, 2023 RayzeBio, Inc., a targeted radiopharmaceutical company developing an innovative pipeline against validated solid tumor targets, reported that the first patient has been dosed in the Phase 3 trial of RYZ101 in patients with SSTR+ gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following prior Lutetium-177 labelled somatostatin analogue therapy (Press release, RayzeBio, MAY 31, 2023, View Source [SID1234632315]).

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"Patients with GEP-NETs have very limited options upon progression after Lutetium-177 labelled somatostatin analogue therapy," said Dr. Thomas Hope, M.D., Vice Chair of Clinical Operations and Strategy in the Department of Radiology. "With existing results using Actinium-225 DOTATATE suggesting clinical benefit, we are excited to be moving this therapy forward in the ACTION-1 study."

The Phase 3 trial is a global study and expected to enroll 210 patients, randomized 1:1 between RYZ101 and investigator’s choice of standard of care (SOC), which includes everolimus, sunitinib, or high-dose long-acting SSAs. The primary endpoint for the trial is progression free survival (PFS). Patients randomized to SOC are allowed to crossover to RYZ101 upon disease progression.

"We are very encouraged by the continued interest in and potential of RYZ101. I look forward to working with the GEP-NET community to advance RYZ101 in this important therapeutic indication. RYZ101 was well tolerated in the Phase 1b trial and we look forward to providing updates on efficacy from the Phase 1b trial even as we continue to enroll patients in the Phase 3 trial," said Susan Moran, M.D., M.S.C.E., Chief Medical Officer of RayzeBio.

About gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors with an incidence of approximately 18,000 patients annually in the United States. Many GEP-NETs follow an indolent disease course and thus the prevalence of patients with GEP-NETs in the United States is several fold that of the incidence. The prognosis for patients with GEP-NET tumors depends on tumor grade and other histopathologic characteristics. Approximately 80% of GEP-NETs express the somatostatin receptor type 2 (SSTR2). Lutathera is a targeted radiopharmaceutical therapy comprised of a somatostatin analog peptide labeled with the beta-emitting radioisotope Lutetium-177 (Lu177), which received regulatory approval for treatment of adult patients with SSTR+ GEP-NETs in Europe and the United States in 2017 and 2018, respectively. However, most patients who receive Lu177-based somatostatin therapies eventually experience tumor progression and have limited subsequent treatment options.

About RYZ101

RYZ101 is an investigational targeted radiopharmaceutical therapy, designed to deliver a highly potent radioisotope, Actinium-225 (Ac225), to tumors expressing SSTR2. RYZ101 is being evaluated in clinical studies for patients with SSTR+ GEP-NETs who have previously been treated with Lu177-based somatostatin therapies and also in patients with newly diagnosed extensive stage small cell lung cancer. Details of the studies can be found at View Source and View Source

Ac225 for the study was provided by multiple sources including the U.S. Department of Energy Isotope Program.