On May 19, 2023, Enzo Biochem, Inc. (the "Company") reported to have entered into a Securities Purchase Agreement (the "Purchase Agreement") with each of the purchasers that are parties thereto (each, including its successors and assigns, a "Purchaser" and collectively, the "Purchasers") and JGB Collateral, LLC, a Delaware limited liability company, as collateral agent for the Purchasers (the "Agent") (Filing, 8-K, Enzo Biochem, MAY 22, 2023, View Source [SID1234631911]). Pursuant to the Purchase Agreement, the Company agreed to sell to the Purchasers (i) 10% Original Issue Discount Secured Convertible Debentures (the "Debentures") with an aggregate principal amount of $7,608,696 and (ii) warrants to purchase up to 1,000,000 shares of the Company’s common stock, par value $0.01 per share (the "Common Stock"), for an exercise price of $2.31 per share, the average of the three (3) daily volume weighted average prices of the Common Stock as defined in the Purchase Agreement ("VWAP") prior to the closing date (the "Warrants"), subject to adjustments as set forth in the Warrants, for a total purchase price of $7,000,000. The Purchase Agreement contains customary representations, warranties and covenants. The transactions contemplated by the Purchase Agreement were consummated on May 19, 2023.

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Debentures

The Debentures bear interest at a rate of 10% per annum (which interest rate is increased to 18% per annum five days after the occurrence and continuance of an Event of Default (as defined in the Debentures)), have a maturity date of May 20, 2024 and are convertible, at any time after their issuance date at the option of the Purchasers, into shares of Common Stock at a conversion price equal to $3.01 per share (the "Conversion Price"), subject to adjustment as set forth in the Debentures. Following the consummation of the Company’s sale of substantially all of the assets and business of Enzo Clinical Labs, Inc., a wholly-owned subsidiary of the Company, to Laboratory Corporation of American Holdings pursuant to the Asset Purchase Agreement, dated March 16, 2023, and as further described in the Company’s definitive Proxy Statement on Schedule 14A filed with the U.S. Securities and Exchange Commission on April 24, 2023 (the "Asset Sale"), the Company shall either, at the option of the Company upon written notice delivered to the Purchasers within three (3) trading days after the consummation of the Asset Sale, (i) prepay $4,000,000 of the outstanding principal amount of the Debentures (to be applied pro rata among the outstanding Debentures based on the relative outstanding principal balance of each Debenture) or (ii) deposit $4,000,000 in cash, as collateral for the Company’s obligations, into a deposit account subject to a deposit account control agreement, among the Company, the depository bank and the Agent and otherwise acceptable to Agent (in its sole absolute discretion) in form and substance.

The Company’s obligations under the Debentures may be accelerated, at the Purchasers’ election, upon the occurrence of certain customary events of default. In the event of a default and acceleration of the Company’s obligations, the Company would be required to pay the greater of (i) the outstanding principal amount of the Debentures, all accrued and unpaid interest, plus the amount of additional interest that would accrue on such principal through the date of maturity, divided by the conversion price on the date accelerated payment is either (A) demanded (if demand or notice is required to create an Event of Default) or otherwise due or (B) paid in full, whichever has a lower conversion price, multiplied by the VWAP on the date the accelerated payment is either (x) demanded or otherwise due or (y) paid in full, whichever has a higher VWAP, or (ii) 130% of the outstanding principal amount of the Debentures, plus all accrued and unpaid interest, plus the amount of additional interest that would accrue on such principal through the date of maturity. Such accelerated payment would also include all other amounts, costs, expenses or liquidated damages due under the Debentures. The Debentures contain customary representations, warranties and covenants including among other things and subject to certain exceptions, covenants that restrict the Company from incurring additional indebtedness, creating or permitting liens on assets, amending its charter documents and bylaws, repurchasing or otherwise acquiring more than a de minimis number of its Common Stock or equivalents thereof, repaying outstanding indebtedness, paying dividends or distributions, assigning or selling certain assets, making or holding any investments, and entering into transactions with affiliates.

Security Agreement and Subsidiary Guarantees

In connection with the Purchase Agreement, on May 19, 2023, the Company, certain of the Company’s domestic subsidiaries ("Guarantors"), the Purchasers and the Agent entered into a Security Agreement (the "Security Agreement"), pursuant to which the Company and the Guarantors granted, for the benefit of the Purchasers, to secure the Company’s obligations under the Purchase Agreement and the Debentures, (i) second-priority liens on certain collateral (the "SLR Collateral") that secures on a first-priority basis the Revolving Loan and Security Agreement between the Company, as borrower, and Gemino Healthcare Finance, LLC d/b/a SLR Healthcare ABL, as lender (the "Credit Facility"), and (ii) first-priority liens on the collateral (the "Non-SLR Collateral" and together with the Non-SLR Collateral, the "Collateral") that does not secure the Credit Facility, in each case subject to permitted liens described in the Indenture. Upon an event of default under the Security Agreement, subject to the security interests under the Credit Agreement, the Purchasers may, among other things, take possession of the Collateral and enter any premises where the Collateral, or any part thereof, is or may be placed and remove the Collateral. In addition, on May 19, 2023, the Company and all of the Guarantors entered into Subsidiary Guarantees (the "Subsidiary Guarantees"), pursuant to which they guaranteed all of the Company’s obligations under the Purchase Agreement and the Debentures.

Warrants

The Warrants are exercisable for five years from May 19, 2023, at an exercise price of $2.31 per share, which is the average of three (3) daily VWAPs prior to the closing date, subject, with certain exceptions, to adjustments in the event of stock splits, dividends, subsequent dilutive offerings and certain fundamental transactions, as more fully described in the Warrant.

If, at the time a Purchaser exercises its Warrant, there is no effective registration statement available for an issuance of the shares underlying the Warrant to the Purchasers, then in lieu of making the cash payment otherwise contemplated to be made to the Company upon the exercise of the Warrant, the Purchaser may elect to receive upon exercise (either in whole or in part) on a cashless basis the net number of shares of Common Stock determined according to a specified formula (as set forth in the Warrant).

Registration Rights Agreement

In connection with the Purchase Agreement, on May 19, 2023, the Company and the Purchasers entered into a Registration Rights Agreement, pursuant to which the Company is obligated to register the shares of Company Common Stock issuable upon exercise of the Debentures and the Warrants by June 19, 2023 (the "Registration Deadline"). If the Company fails to meet the Registration Deadline or maintain the effectiveness of the Registration Statement for the required effectiveness period, subject to certain permitted exceptions, the Company will be required to pay liquidated damages to the Purchasers. The Company also agreed, among other things, to indemnify the selling holders under the Registration Statement from certain liabilities and to pay all fees and expenses incident to the Company’s performance of or compliance with the Registration Rights Agreement.

The foregoing descriptions of the terms of the Purchase Agreement, Debentures, Security Agreement, Subsidiary Guarantees, Warrants and Registration Rights Agreement and the transactions contemplated thereby do not purport to be complete and are qualified in their entirety by reference to the Purchase Agreement, form of Debenture, Security Agreement, form of Subsidiary Guarantee, form of Warrant and Registration Rights Agreement, which are included as Exhibits 10.1, 4.1, 10.3, 10.4, 4.2 and 10.2, respectively, to this Current Report on Form 8-K and are incorporated herein by reference.

On May 19, 2023 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing first-in-class1 therapeutics that combine both targeted and immune-mediated mechanisms, reported that the Compensation Committee of the company’s Board of Directors granted one employee a nonqualified stock option to purchase 12,600 shares of its common stock with an exercise price equal to the closing price of Tempest’s common stock on May 15, 2023, the grant date of the award (Press release, Tempest Therapeutics, MAY 19, 2023, View Source [SID1234631891]). The stock option was granted as an inducement award material to the individual entering into employment with Tempest, in accordance with Nasdaq Listing Rule 5635(c)(4).

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The stock option will vest over a four-year period, with 25% of the option vesting on the first anniversary of the employee’s start date, and 1/48th of the total shares vesting monthly thereafter, subject to continued employment on each vesting date. The option is subject to the terms and conditions of Tempest’s Amended and Restated 2019 Equity Incentive Plan and the stock option agreement covering the grant.

On May 19, 2023 Rznomics Inc., a South Korea based biopharmaceutical company specialized in the development of RNA-based gene therapeutics, reported to have recently received Phase 1/2a IND approval from the U.S FDA on May 6th for its Glioblastoma Multiforme (GBM) treatment called RZ-001 and thus has achieved an important milestone for the company and the RNA editing field. RZ-001 initially obtained the IND approval with the indication for HCC, but Rznomics also found the great pre-clinical efficacy in GBM models and submitted the IND for the GBM (Press release, Rznomics, MAY 19, 2023, View Source [SID1234631887]). Being the first U.S. FDA-approved ribozyme-based RNA reprogramming approach to be evaluated in patients, RZ-001, a gene therapy approach utilizing the company’s proprietary trans-splicing ribozyme-based RNA reprogramming and editing technology, is a replication-incompetent adenoviral vector that expresses an hTERT targeting ribozyme with multiple additional MoA to treat GBM patients.

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The trans-splicing ribozyme is derived from the self-splicing Tetrahymena group I intron, which both recognizes and reprograms the target RNA into the therapeutic transcript of interest. Ribozyme-based RNA editing technology developed by Rznomics has unique features, differentiating it from other nucleic acid-based editing approaches, as follows: (1) A single RNA molecule is catalytically capable of both suppressing target RNA expression and simultaneously expressing a therapeutic RNA. Thus, no potentially antigenic proteins or cofactors are required. (2) Safety can be improved by selectively inducing therapeutic RNA expression only in cells/tissues where the target gene is expressed. (3) Therapeutic gene expression can be regulated proportionally to endogenous cellular target RNA levels. (4) Editing occurs at the RNA level, not the genomic level, thus eliminating concerns about genomic toxicity and eternal genome changes. (5) Indications with multiple mutation sites scattered throughout a target RNA can be edited with a single RNA designed to react upstream of all mutations and by replacing and editing large stretches of RNA. (6) Additional safety can be conferred by building control mechanisms into the ribozyme itself, without the need to modulate intrinsic cellular mechanisms or external proteins.

More specifically, RZ-001 engenders effective anti-GBM activity by suppressing hTERT expression selectively in cancer cells, which over-express hTERT, and simultaneously inducing a cytotoxic effect by trans ligating an HSVtk-encoding sequence into the reprogrammed hTERT mRNA. Moreover, the result of such editing efficiently induces immune cell infiltrations into GBM tumors and hampers angiogenesis in the tumor tissues in preclinical animal models. (View Source). The Phase 1/2a clinical trial will be a dose escalation/expansion study to assess the safety and tolerability of RZ-001 and to determine the most effective dose with the least toxicities of RZ-001 in recurrent GBM patients without extracranial metastases.

"It’s a monumental achievement of Rznomics that RZ-001, the first trans-splicing ribozyme therapy at the front of our therapeutic pipeline, has successfully received another IND approval in the United States with the indication for the GBM. I am really grateful that RZ-001 earned the opportunity to potentially fulfill the unmet needs of GBM patients. Through the advanced development phase, I hope Rznomics can provide more new therapeutic options to patients suffering from intractable diseases. Rznomics will further expand our pipeline by targeting indications with highly unmet medical needs for which the unique characteristics of our platform technology may be the most competitively applied," said Dr. Seong-Wook Lee, Ph.D., CEO, and founder of Rznomics.

In addition to the HCC & GBM, Rznomics is developing ribozyme-based RNA editing treatments for Alzheimer’s disease (RZ-003) and inherited retinal dystrophies, called Retinitis pigmentosa (RZ-004).

On May 19, 2023 KaliVir Immunotherapeutics, Inc., a biotech company developing cutting-edge, multi-mechanistic oncolytic viral immunotherapy programs, reported the presentation of new data on its lead pre-clinical candidate VET3-TGI at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 26th Annual Meeting (Press release, KaliVir Immunotherapeutics, MAY 19, 2023, View Source;cell-therapy-asgct-annual-meeting-301829030.html [SID1234631886]).

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VET3-TGI is based on KaliVir’s unique Vaccinia Enhanced Template (VET) platform, capable of generating potent novel oncolytic vaccinia viruses with modifications to maximize viral replication and enhance intravenous delivery and spread. Modifications grant VET3-TGI the expression of CXCR3, IL-12 and a TGF-β inhibitor, allowing for efficient trafficking to the tumor, activation of anti-tumor immune responses and the overcoming of local immunosuppressive activity.

The functionality and therapeutic activity of VET3-TGI were tested in multiple models, and the mechanism of action and toxicity profile were assessed. VET3-TGI was compared to control virus in three pre-clinical in vivo tumor models, and demonstrated potent therapeutic activity, including 100% complete responses, even at several logs below equivalent clinical doses and in the presence of pre-existing anti-viral immunity. Profound changes in the tumor microenvironment (TME) were observed in VET3-TGI treated mice, including polarization to a type-1 immune response and recruitment of cytotoxic T cells. Analysis of gene expression profiles revealed that VET3-TGI treatment was associated with a dramatic increase in type-1 inflammatory chemokines, and a concomitant decrease in the expression of TGFβ1-associated genes that are involved with immuno-suppression. Compared to control virus-treated mice, VET3-TGI showed improved delivery to tumors following systemic administration, as well as reduced systemic toxicity.

"This new in vivo data is very encouraging and is a further validation of VET3-TGI as our lead pre-clinical candidate," said Stephen Thorne, PhD, CSO and co-founder of KaliVir. "These results build upon our already robust in vitro data as we expand into the next phase to develop a human version of the virus for efficacy and toxicology testing."

Presentation details

Date:

Friday, May 19th 5:15 PM – 5:30 PM PT

Title:

Novel Oncolytic therapy VET3-TGI restricts TGFβ1 and augments Type-1 immune response in TME, leading to superior therapeutic efficacy in multiple preclinical tumor models.

Presented by:

Ravikumar Muthuswamy, Ph.D. Director of Immunology, KaliVir Immunotherapeutics

Location:

Los Angeles Convention Center, West Hall, Room 501 ABC

On May 19, 2023 Genome & Company (CEOs: Pae, Jisoo, Park, Hansoo), a global leading microbiome therapeutics developer, reported that this phase II trial (NCT05419362) will continue without modifications to move on to the second stage, based on the positive result of the interim analysis (Press release, Genome & Company, MAY 19, 2023, View Source [SID1234631885]).

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Using a single-strain bacteria in combination with avelumab (Bavencio) from Merck KGaA, Darmstadt, Germany and Pfizer Inc., it is the first time to show positive antitumor activity per ORR in Phase II trial. The detailed results will be presented at a conference in the second half of 2023.

On the basis of these results and in accordance with the predetermined hypothesis of the interim analysis, Genome & Company highly expect that the evidence for treatment with GEN-001 plus avelumab as a 3rd line of therapy for GC/GEJ will be strongly established.

This is a Phase II study to evaluate the safety and efficacy of GEN-001 plus Avelumab as a ≥3rd line treatment for PD-L1 positive GC/GEJ patients regardless of prior immune-oncology (IO) treatment. Following enrollment of the 21st patient, a pre-planned interim analysis was conducted and results were reviewed by an independent data monitoring committee (IDMC).

As the observed ORR met the pre-determined criteria together with no safety concerns, the IDMC recommended to continue with the second stage without modifications and enroll additional 21 patients. The detailed results will be presented at an Oncology conference in the second half of 2023. The top-line data of the final analysis from Phase II are expected in the second half of next year.

Professor Jeeyun Lee, the principal investigator of clinical trials from the Hematology and Oncology Division at Samsung Medical Center, stated, "There is a strong unmet medical need to establish 3rd line of therapy for GC/GEJ patients compared with the establishing 1st and 2nd lines of therapy. Hence, the pre-planned interim result of this trial is quite interesting. We continue to enroll patients and look forward to seeing the final analysis of this trial soon."

The CEO of Genome & Company, Pae, Jisoo, stated, "We attach great significance to presenting data-driven results for the first time through Phase II clinical trials on gastric cancer patients using the immuno-oncology microbiome therapeutic ‘GEN-001’ in combination with avelumab from Merck KGaA, Darmstadt, Germany and Pfizer Inc." and "we intend to obtain phase II clinical data for ‘GEN-001’ within next year and to discuss a licensing agreement with partners or global big pharmaceutical companies."

It is also worth noting that GEN-001 is currently undergoing phase 2 clinical trial with combination therapy with MSD’s pembrolizumab (Keytruda) for patients with advanced biliary tract cancer. The first patient in will be initiated in the second half of this year. To expand treatment options for advanced biliary tract cancer with high unmet medical needs, Genome & Company recently requested approval from the Ministry of Food and Drug Safety (MFDS) in South Korea to amend the protocol.