On April 15, 2024 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to achieve the first approval for an ophthalmic formulation of bevacizumab for the treatment of retinal diseases in the US and the EU, reported that it has closed its previously announced private placement with Syntone Ventures, LLC, an existing stockholder, for upfront gross proceeds of approximately $5.0 million from the issuance and sale of shares of the Company’s common stock and accompanying warrants, before deducting offering expenses (Press release, Outlook Therapeutics, APR 15, 2024, View Source [SID1234642072]). In addition, Outlook Therapeutics has the potential to receive additional gross proceeds of up to $8 million upon the full cash exercise of the warrants issued in the private placement, before deducting offering expenses.

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About the Private Placement

Pursuant to the securities purchase agreement entered into on January 24, 2024, Outlook Therapeutics issued to Syntone an aggregate of 714,286 shares of common stock and accompanying warrants to purchase an aggregate of 1,071,429 shares of common stock, at a price of $7.00 per share and accompanying warrant to purchase one and one-half shares of common stock. The warrants have an exercise price of $7.70 per share and are exercisable only for cash until their expiration on the fifth anniversary of the issuance date. The warrants include a feature that allows Outlook Therapeutics to require Syntone to cash exercise the warrants if certain stock price and milestone conditions are met.

All of the securities in the private placement were offered by the Company.

Outlook Therapeutics intends to use the net proceeds from the private placement to fund its ONS-5010 clinical development programs, including the ongoing NORSE EIGHT clinical trial, and for working capital and other general corporate purposes.

As previously disclosed, Outlook Therapeutics also entered into, and received proceeds from, a securities purchase agreement with Great Point Partners, LLC, GMS Ventures, and other investors to purchase $60 million in shares of common stock and warrants on substantially the same terms as the private placement.

The offer and sale of the foregoing securities were made by Outlook Therapeutics in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and/or Regulation D promulgated thereunder, and such securities have not been registered under the Act or applicable state securities laws. Accordingly, such securities may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws. Outlook Therapeutics has agreed to file a resale registration statement with the U.S. Securities and Exchange Commission for purposes of registering the resale of the common stock issued or issuable in connection with the private placement.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities described herein 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.

About ONS-5010 / LYTENAVA (bevacizumab-vikg, bevacizumab gamma)

ONS-5010/LYTENAVA is an investigational ophthalmic formulation of bevacizumab under development as an intravitreal injection for the treatment of wet AMD and other retinal diseases. Because no FDA or European Commission approved ophthalmic formulations of bevacizumab are available currently, clinicians wishing to treat retinal patients with bevacizumab have had to use repackaged IV bevacizumab provided by compounding pharmacies—products that have known risks of contamination and inconsistent potency and availability. If approved, ONS-5010/LYTENAVA would provide an approved option for physicians to treat wet AMD.

Bevacizumab-vikg/bevacizumab gamma is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab-vikg to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.

On April 15, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 in patients with advanced solid tumors with EGFR and HER2 exon 20 alterations or HER2 amplifications (Press release, ORIC Pharmaceuticals, APR 15, 2024, View Source [SID1234642071]). Based upon these data, ORIC selected the two provisional recommended Phase 2 dose (RP2D) levels of ORIC-114 at 80 mg and 120 mg QD, which are being further evaluated in three dose expansion cohorts for dose optimization and final RP2D selection. These expansion cohorts have now been initiated in patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 (EGFR exon 20 inhibitor naïve), HER2 exon 20, or EGFR atypical mutations. The company also announced the initiation of an extension cohort for the treatment of patients with first-line, treatment-naïve EGFR exon 20 NSCLC.

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"Following the positive dose escalation data reported at ESMO (Free ESMO Whitepaper) 2023, we are excited to announce the advancement of ORIC-114 into Phase 1b dose expansion," said Pratik Multani, M.D., chief medical officer of ORIC. "Encouraging findings from the Phase 1b dose escalation phase of the trial demonstrated a potential best-in-class profile for ORIC-114, with notable systemic responses and CNS responses, as well as a favorable safety profile, in heavily pre-treated patients. Based on these results, we have identified the two dose levels that we are now advancing into Phase 1b expansion cohorts to determine the final RP2D for further development, including potential registrational cohorts. At the request of many of our investigators and because of the lack of other CNS-active agents against EGFR exon 20, we are also extending our trial to include a cohort evaluating first-line, treatment-naïve NSCLC. We are hopeful that the expansion portion of the trial will validate and build upon the encouraging efficacy seen in the dose escalation, and plan to report results in the first half of 2025."

The Phase 1b dose escalation part of the trial evaluated ORIC-114 in patients with advanced solid tumors with EGFR and HER2 exon 20 alterations or HER2 amplifications. Patients previously treated with an exon 20 targeted agent were eligible, including patients with CNS metastases that were either treated or untreated but asymptomatic. Nearly all other clinical trials with EGFR exon 20 inhibitors severely restricted the eligible patient population and excluded patients with active or untreated brain metastases and patients previously treated with an EGFR exon 20 inhibitor. The primary objectives were to determine the provisional RP2D, and additional objectives included characterization of the safety, tolerability, pharmacokinetic, and preliminary antitumor activity.

The Phase 1b expansion portion of the trial will evaluate the safety and efficacy of ORIC-114 at the provisional RP2D levels of 80 mg and 120 mg QD in patients with mutated NSCLC, including EGFR exon 20 (EGFR exon 20 inhibitor naïve), HER2 exon 20, and EGFR atypical mutations. The primary objectives are to determine the RP2D, and additional objectives include assessment of efficacy in terms of objective response rate, duration of response and progression-free survival, including intracranial activity, as well as further characterization of the safety profile of ORIC-114.

About ORIC-114
ORIC-114 is a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations, making it a promising therapeutic candidate to address the unmet medical need of having both meaningful systemic as well as CNS antitumor activity.

On April 15, 2024 INOVIO Pharmaceuticals, Inc. (Nasdaq: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported the pricing of an underwritten offering of 2,536,258 shares of its common stock at an offering price of $7.693 per share and pre-funded warrants to purchase 2,135,477 shares of its common stock at an offering price of $7.692 per pre-funded warrant, in each case before underwriting discounts and commissions (Press release, Inovio, APR 15, 2024, View Source [SID1234642070]). Gross proceeds to INOVIO from the offering are expected to be approximately $36 million, before deducting underwriting discounts and commissions and estimated offering expenses payable by INOVIO. The offering is expected to close on or about April 18, 2024, subject to customary closing conditions. All of the securities are being sold by INOVIO.

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The offering was led by Deep Track Capital.

Oppenheimer & Co. and Citizens JMP are acting as joint book-running managers for the offering.

The securities were offered by INOVIO pursuant to an effective shelf registration statement previously filed by INOVIO with the Securities and Exchange Commission (SEC). A final prospectus supplement and accompanying prospectus related to the offering will be filed with the SEC, and will be available on the SEC’s website located at View Source When available, copies of the final prospectus supplement and the accompanying prospectus relating to the offering may also be obtained by contacting: Oppenheimer & Co. Inc., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, NY 10004, by telephone at (212) 667-8055, or by email at [email protected]; or Citizens JMP Securities, LLC, 600 Montgomery Street, Suite 1100, San Francisco, CA 94111, by telephone at (415) 835-8985, or by email at [email protected].

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 April 15, 2024 Immix Biopharma, Inc. (Nasdaq: IMMX) ("ImmixBio", "Company", "We" or "Us" or "IMMX"), a clinical-stage biopharmaceutical company trailblazing cell therapies in AL Amyloidosis and other autoimmune diseases, reported that updated NXC-201 clinical data has been selected for presentation at the upcoming 27th Annual Meeting of The American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) to be held in Baltimore May 7-11, 2024 (Press release, Immix Biopharma, APR 15, 2024, View Source [SID1234642069]).

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"We are delighted to present continued clinical progress developing what we believe is the only CAR-T in AL Amyloidosis at the upcoming 27th Annual Meeting of The American Society of Gene & Cell Therapy," said Polina Stepensky, M.D., Director of the Hadassah Medical Organization’s Department of Bone Marrow Transplantation and Immunotherapy for Adults and Children, and principal study investigator for the NEXICART-1 Phase 1b/2a clinical trial of NXC-201. "A potential one-time treatment such as CAR-T NXC-201 for relapsed/refractory AL amyloidosis patients would be a welcome option for this devastating disease."

Oral Presentation:

Title: "Academic BCMA-CART cells (HBI0101), a promising approach for the treatment of LC Amyloidosis"

Oral Presentation Date/Time: Friday May 10, 2024 8:45 am – 9:00am Eastern Time
Event: 27th Annual Meeting of The American Society of Gene and Cell Therapy, Baltimore, MD

Session Title: Late-Breaking Abstracts II

Location: Baltimore Convention Center, Baltimore, MD

About NEXICART-1

NEXICART-1 (NCT04720313) is an ongoing Phase 1b/2a, open-label study evaluating the safety and efficacy of NXC-201 (formerly HBI0101), in adults with relapsed/refractory multiple myeloma and AL amyloidosis.

The primary objective of the Phase 1b portion of the study is to characterize the safety and confirm the Maximally Tolerated Dose (MTD) and Phase 2 dose of NXC-201. The Phase 2 portion of the study will evaluate the efficacy and safety of NXC-201 with endpoints of overall survival, progression-free survival and response rates according to International Myeloma Working Group (IMWG) Uniform Response Criteria.

The Phase 1b portion of the ongoing Phase 1b/2 clinical trial has been successful in determining the recommended Phase 2 dose (RP2D) of 800 million CAR+T cells. The expected primary endpoint for the Phase 2 portion of the ongoing Phase 1b/2a clinical trial of NXC-201 in relapsed/refractory AL Amyloidosis is overall response rate. ImmixBio plans to submit data to the FDA in AL amyloidosis once 30-40 patients are treated with NXC-201.

About NXC-201

We believe NXC-201 (formerly HBI0101) is the only "Single-Day CRS" CAR-T cell therapy that is uniquely suited to target AL Amyloidosis and other autoimmune diseases. It is being studied in a comprehensive clinical development program for the treatment of patients with relapsed/refractory AL amyloidosis, and expanding into other autoimmune indications. These trials build on a robust NXC-201 clinical dataset initiated in February 2021. NXC-201 has been awarded Orphan Drug Designation (ODD) by the FDA in both AL Amyloidosis and multiple myeloma, and awarded EU ODD by the EMA in AL Amyloidosis.

About AL Amyloidosis

AL amyloidosis is a systemic disorder caused by an abnormality of plasma cells in the bone marrow. Misfolded amyloid proteins produced by plasma cells cause buildup in and around tissues, nerves and organs, gradually affecting their function. This can cause progressive and widespread organ damage, and high mortality rates.

U.S. observed prevalence of relapsed/refractory AL Amyloidosis is growing 12% per year according to Staron, et al Blood Cancer Journal, estimated to reach 33,277 patients in 2024. The Amyloidosis market was $3.6 billion in 2017, expected to reach $6 billion in 2025, according to Grand View Research.

On April 15, 2024 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported that a paper detailing the development of its "off-the-shelf" neoantigen platform, SLATE, recently published in Nature Medicine (Press release, Gritstone Bio, APR 15, 2024, View Source [SID1234642068]). The paper, "A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results," describes a novel immunodominance hierarchy of tumor neoantigens (including KRAS) that Gritstone discovered in Phase 1 translational studies and leveraged to develop SLATE-KRAS, a "pure" KRAS-directed candidate that demonstrated superior immunogenicity to the initial version in a subsequent Phase 2 study and is currently being evaluated in a novel cell therapy-vaccine combination study run by Steven A. Rosenberg of the National Cancer Institute (NCT06253520).

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"The publication of these findings in Nature Medicine highlights the promise of our ‘off-the-shelf’ or shared neoantigen approach in solid tumors, one of the many elements embedded within our mission to develop the world’s most potent vaccines," said Andrew Allen, M.D., Ph.D., Co-founder, President, and Chief Executive Officer of Gritstone bio. "Our team’s innovative work to develop, optimize and validate SLATE positions Gritstone with two promising platforms to execute against our neoantigen-directed approach to oncology. It also enabled the pioneering collaboration that we are currently advancing with Dr. Rosenberg of the NCI, a luminary in the field. SLATE is ready for ‘plug and play’ application across a spectrum of solid tumors and could serve as a great complementary platform to GRANITE, our personalized vaccine program. We continue to have great conviction that both approaches could unlock new levels of immune responses for patients with solid tumors."

"This important publication underscores that a deep understanding of the mechanism and performance of therapeutic neoantigens in humans is likely critical for success in the promising field of neoantigen-directed immunotherapy. It also demonstrates our ability to select tumor antigens and optimize cassette design to elicit a potent antigen-specific immune response," said Karin Jooss, Ph.D., Executive Vice President, and Head of R&D at Gritstone bio. "We believe we have a leading understanding of the hierarchy of antigen presentation and competition – a great example outlined in this paper, where we took SLATE from bench to bedside to bench, and back – and have applied that understanding to optimize the design of our oncology vaccines. The learnings and techniques described add to Gritstone’s already robust body of clinical insights to drive potent tumor-specific T cell responses to neoantigens, a unique potential advantage in the field."

Results from the SLATE 1/2 Study
The data published in Nature Medicine report the interim safety, tolerability and immunogenicity results from the Phase 1 portion of the Phase 1/2 clinical trial (NCT03953235) assessing the off-the-shelf vaccine SLATEv1 in patients with advanced/metastatic solid tumors. SLATEv1 utilizes a heterologous ChAd68 followed by samRNA-based vaccine regimen encoding 20 shared neoantigens targeting multiple recurrent mutations in several oncogenes, including KRAS, TP53, BRAF and CTNNB1. Neoantigens were identified using Gritstone bio’s proprietary neoantigen prediction platform, EDGETM, and selected based on shared mutation and matched HLA frequencies in patient populations with solid tumors. Biased T cell responses toward HLA-matched TP53 neoantigens encoded in the vaccine relative to KRAS neoantigens expressed by the patients’ tumors, indicated a previously unknown hierarchy of neoantigen immunodominance that may impact the therapeutic efficacy of multi-epitope shared neoantigen vaccines. These data led to the development of SLATE-KRAS, a vaccine focused on KRAS-derived neoantigens that subsequently was evaluated in the Phase 2 portion of the clinical study. Initial Phase 2 data suggesting an increased vaccine induced T cell response were presented in September 2022 (press release).

To view all of Gritstone bio’s scientific publications, visit gritstonebio.com/publications.

About SLATE ("off-the-shelf" neoantigen vaccine program)
Gritstone’s neoantigen-based vaccine programs, GRANITE (personalized) and SLATE ("off-the-shelf) are engineered to elicit a significant T cell response for patients with solid tumors. Like GRANITE, SLATE uses Gritstone’s proprietary epitope identification platform (EDGE) and vaccine vectors (Chimpanzee Adenovirus and self-amplifying mRNA) to deliver each patient a set of neoantigens that are predicted to drive a T cell response. Unlike GRANITE, SLATE delivers a set of neoantigens that are shared across a subset of cancer patients based on common gene mutations, such as KRAS mutations. In Phase 1/2 study, SLATE-KRAS demonstrated positive results in patients with late-line non-small cell lung cancer and microsatellite stable colorectal cancer. With these results, Gritstone believes the SLATE platform is ready for ‘plug and play’ application across solid tumor indications and shared tumor neoantigen classes.