On April 26, 2022 Isleworth Healthcare Acquisition Corp. (NASDAQ: ISLE) ("Isleworth"), a special purpose acquisition company (NASDAQ: ISLE, ISLEW) and Cytovia Holdings, Inc.("Cytovia"), a biopharmaceutical company empowering natural killer (NK) cells to fight cancer through stem cell engineering and multispecific antibodies reported they have entered into a definitive business combination agreement (Press release, Cytovia Therapeutics, APR 26, 2022, View Source [SID1234612994]). Upon consummation of this combination, Isleworth will be renamed Cytovia Therapeutics, Inc. (the "combined company") and its common stock and warrants are expected to remain listed on NASDAQ under the ticker symbols INKC and INKCW, respectively .

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The combined company will continue Cytovia’s operations and remain focused on developing and manufacturing complementary NK cell and NK engager antibody platforms.

The combined company will be led by Dr. Daniel Teper, the Co-Founder, Chairman, and Chief Executive Officer of Cytovia.

"We are grateful for the strong support from new and existing investors and the team of seasoned entrepreneurs at Isleworth. We expect this transaction to accelerate the execution of Cytovia’s vision to advance NK therapeutics towards a cure for cancer" said Dr. Teper. "We are encouraged by our preclinical data recently presented at AACR (Free AACR Whitepaper), which supports advancing development of our iPSC-derived NK cells (iNK) and Flex-NK cell engagers for the treatment of Hepatocellular Carcinoma."

Bob Whitehead, Isleworth’s CEO, said: "Isleworth evaluated multiple life science companies and was most impressed by the talent and technology assembled by Cytovia. We believe Cytovia is one of the most advanced, innovative cell therapy companies involved with the development of new cancer treatments. Cell therapies in oncology have already brought hope to millions. Cytovia’s approaches could conceivably make similar approaches more conveniently ‘off-the-shelf’ and affordable."

Cytovia’s Therapeutic Approach

Cytovia aims to accelerate patient access to transformational cell therapies and immunotherapies, addressing several of the most challenging unmet medical needs in oncology.

The company focuses on harnessing the innate immune system by developing complementary and disruptive NK-cell and NK-engager antibody platforms. Specifically, Cytovia is developing three types of iNK cells: unedited iNK cells, TALEN gene-edited iNK cells with improved function and persistence, and TALEN gene-edited iNK cells with chimeric antigen receptors (CAR-iNKs) to improve tumor-specific targeting. The second complementary cornerstone technology is a quadrivalent multispecific antibody platform designed to engage NK cells by targeting the NKp46 activating receptor using a proprietary Flex-NK technology.

These two technology platforms are being used to develop treatments for patients with Hepatocellular Carcinoma (HCC) and solid tumors. Clinical studies are expected to initiate by the end of 2022.

Headquartered in Aventura, FL, Cytovia operates R&D laboratories in Natick, MA and a cGMP cell manufacturing facility in Puerto Rico and has scientific partnerships with Cellectis, CytoImmune Therapeutics, the Hebrew University of Jerusalem, INSERM, the New York Stem Cell Foundation, the National Cancer Institute, and the University of California San Francisco (UCSF). Cytovia Therapeutics has recently formed CytoLynx Therapeutics, a strategic partnership focused on research and development, manufacturing, and commercialization activities in Greater China and beyond.

Cytovia Pipeline

Cytovia is the first immune-oncology company with the capabilities to combine gene edited iPSC-derived NK Cell and Flex-NK cell engager antibody platforms to develop the next generation of immunotherapies for both hematological and solid tumors.

Cytovia’s portfolio includes targets and indications with a balanced risk profile.

GPC3 is a promising novel target for solid tumors, particularly hepatocellular carcinoma, where the unmet medical need is most significant. Cytovia’s lead program aims to develop first-in-class HCC therapies targeting GPC3. The initial four product candidates will be evaluated as monotherapies and as combination therapies. CYT-303, Cytovia’s GPC3 Flex-NK engager, is a tri-specific antibody that binds to HCC tumor cells through GPC3 and to NK cells through NKp46 and CD16a. For patients with either an impaired number or function of NK cells, Cytovia will evaluate the addition of iNK cells, CYT-100, to possibly unlock the full potential of this treatment strategy. Cytovia is also developing CYT-150, gene-edited iNK cells, to improve tumor infiltration and cell persistence, that may also be combined with CYT-303. In addition, CYT-503, a GPC3-targeting CAR-iNK cell therapeutic, is designed to improve specificity for tumor targeting. Cytovia expects to file INDs for CYT-303 and CYT-100, followed by INDs for CYT-150 and CYT-503.

CD38 is a well-established clinical and commercial target for Multiple Myeloma. Cytovia is developing CYT-338 and CYT-538 which are, respectively, CD38-targeting Flex-NK cell engagers and CAR-iNK cells for the treatment of Multiple Myeloma in patients that have failed CD38 antibody therapies and agents targeting B-cell maturation antigen (BCMA).

Cytovia is also developing an intracranial EGFR CAR iNK candidate to target both wtEGFR and EGFR vIII to address a significant medical need in the management of the currently untreatable Glioblastoma multiforme.

Cytovia has established collaborations with academic institutions and industry partners including Cellectis for TALEN gene-editing. TALEN gene-editing is a technology pioneered and controlled by Cellectis, a clinical-stage biotechnology company using its gene-editing platform to develop life-saving cell and gene therapies. The TALEN gene-edited patents controlled by Cellectis in the field of iNK and CAR-iNK are licensed from Cellectis by Cytovia and Cytovia holds global development and commercial rights to these patents.

Planned Milestones and Use of Proceeds

Proceeds from private placements (the "PIPE"), funds in Isleworth’s trust account (net of redemptions), and proceeds from other prospective financings, in the aggregate amount of up to one hundred million dollars, would provide Cytovia with capital for up to 2 years to further develop its gene-edited iNK and Flex-NK cell engager technologies. Cytovia plans to focus on multiple milestones, including:

Filing the first two INDs for Flex-NK CYT-303 and iNK CYT-100
Initiating Phase I/II clinical trials to evaluate CYT-303 and CYT-100, alone and in combination, for the treatment of HCC
Obtaining and presenting initial clinical data for CYT-303 and CYT-100 in HCC
Filing INDs for CYT-150 and CYT-503 and initiating Phase I/II clinical trials
Continuing to enhance iNK & Flex-NK technologies and advance the pipeline with multiple therapeutic candidates
Summary of Transaction

The transaction would value the combined company at a pro forma equity value of $602 million, assuming a $10 per share price, no Isleworth stockholder redemptions and no additional financing obtained prior to the closing of the transaction. As a result of the transaction, the combined company would have up to $227 million in gross proceeds from a combination of approximately $207 million in cash held in Isleworth’s trust account (assuming no Isleworth stockholders exercise their redemption rights at closing) and $20 million from PIPE financing of new investors, and without considering the proceeds of any additional prospective financing.

All existing Cytovia equity holders will roll the entirety of their equity holdings into the combined company and are expected to hold approximately half of the issued and outstanding equity of the combined company immediately following the closing (assuming no Isleworth shareholders exercise their redemption rights at closing).

The transaction, which has been approved by each of Isleworth’s and Cytovia’s Boards of Directors, is expected to be completed in the third quarter of 2022, subject to approval by Isleworth’s and Cytovia’s shareholders and satisfaction, or the waiver of, customary closing conditions identified in the business combination agreement.

Isleworth and Cytovia have agreed in the business combination agreement to take all necessary action to cause the board of directors of the combined company immediately following the closing to consist of seven directors, of whom two individuals will be designated by Isleworth and five individuals will be designated by Cytovia. Each designee will meet the director qualification and eligibility criteria of the Nominating and Corporate Governance committee of the board of directors of Isleworth, and a number of Cytovia designees will qualify as independent directors as determined by the board of directors of Isleworth such that a majority of the directors as of immediately following the closing will qualify as independent directors.

I-Bankers Securities, Inc. is serving as capital markets advisor and placement agent to Isleworth. Truist Securities is acting as financial advisor, placement agent and capital markets advisor to Cytovia. BTIG LLC is acting as capital markets advisor to Cytovia.

Cooley LLP is serving as legal advisor to Cytovia. ArentFox Schiff LLP is serving as legal advisor to Isleworth. Goodwin Procter is serving as legal advisor to Truist Securities in its role as placement agent.

On April 26, 2022 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that it has filed a clinical trial application with the Human Research Ethics Committee (HREC) in Australia in order to initiate the Phase I ATRIUM trial of ATG-018 in patients with advanced solid tumors and hematologic malignancies (Press release, Antengene, APR 26, 2022, View Source [SID1234612993]).

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The primary objective of the study is to evaluate the safety and tolerability of ATG-018 as monotherapy to determine the appropriate dose for Phase II studies and assess preliminary efficacy, if available; the secondary objective is to characterize the pharmacology of ATG-018.

ATG-018 is an orally available, potent, selective small molecule ATR inhibitor. ATG-018 inhibits the ATR (ataxia telangiectasia mutated and Rad3-related) kinase, thus limiting cancer cells’ ability to repair damaged DNA, in a mechanism also known as synthetic lethality.

Dr. Bo Shan, Chief Scientific Officer of Antengene commented, "ATG-018, one of Antengene’s first in-house programs to reach the clinic, targets the DDR pathway that is deregulated in many cancers. DDR inhibitors represent a promising area of drug development and clinical research in oncology, especially in resistant or advanced diseases. The differentiated profile of ATG-018 may enable it to be used as monotherapy and open the door for novel collaborations and combination regimens that could benefit cancer patients around the world."

Dr. Kevin Lynch, Chief Medical Officer of Antengene continued, "Antengene is very excited to submit the ATG-018 Phase I protocol for HREC review, based on its solid preclinical data package including efficacy as a monotherapy in solid tumor models, oral bio-availability and potential biomarkers. The use of biomarker-informed studies may facilitate clinical trial enrollment and provide an additional tool to monitor patients during the trial. As we prepare for the start of this important study, I want to thank all of the investigator sites for their support and enthusiasm, and everyone in Antengene’s R&D organization for their dedication in the preparation for this study."

About the ATRIUM Trial

The ATRIUM trial is a Phase I multi-center, open-label, dose finding study of ATG-018 monotherapy in patients with advanced solid tumors or hematologic malignancies. The primary objective of the study is to evaluate the safety and tolerability of ATG-018 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and/or biologically effective dose of ATG-018 monotherapy and preliminary efficacy, if available; the secondary objective is to characterize the pharmacology of ATG-018. As a Phase I study, there will be intensive safety monitoring throughout the trial.

About ATG-018

Developed by the internal R&D Team at Antengene, ATG-018 is an oral, potent, selective small molecule inhibitor targeting ataxia telangiectasia and Rad3-related (ATR) kinase. ATR kinase belongs to the phosphoinositide 3 kinase-related family. Inhibiting ATR kinase leads to increased accumulation of single-strand DNA breaks, particularly meaningful for tumor cells which rely on DNA damage repair (DDR). Preclinical studies have demonstrated that ATR inhibitor monotherapy or combination with other drugs (including DDR agents) could be promising therapeutic strategies for solid tumors (including gastric, esophageal, squamous cell carcinoma) and hematologic malignancies (chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma [DLBCL] and multiple myeloma [MM]).

According to a preclinical poster presented at AACR (Free AACR Whitepaper) 2022, ATG-018 has demonstrated potent in vitro and in vivo monotherapy efficacy in solid tumor/hematologic cancer models with certain homologous recombination deficiencies. These data were supported by a series of genetic alterations that correlated with ATG-018 sensitivity and could be potential predictive biomarkers. Taken together, these data suggest that ATG-018 could be a promising therapeutic agent for patients with such homologous recombination deficiencies/genetic alterations.

ATG-018 is a development stage product candidate and is not approved by any regulatory agency. Antengene has global rights to ATG-018.

On April 26, 2022 Ambrx Biopharma Inc., or Ambrx, (NYSE: AMAM), a clinical stage biopharmaceutical company using an expanded genetic code technology platform to create Engineered Precision Biologics, reported financial results for the full year ended December 31, 2021 (Press release, Ambrx, APR 26, 2022, View Source [SID1234612992]).

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"We have made great progress in advancing our engineered precision biologics and clinical pipeline in recent months. We continue to transition preclinical candidates into the clinic and anticipate submitting another IND to the U.S. FDA in 2022. Ambrx has several potential key milestones coming up in the mid-year and into the second half of this year including initiating two clinical trials of ARX788 for Her2+ breast cancer in the neoadjuvant setting, a single agent and a combination trial with an anti-PD-1 agent, and a clinical trial of ARX305 in renal cell carcinoma (RCC) and other cancers," commented Feng Tian, Ph.D., Chairman of the Board, President and CEO of Ambrx. "Ambrx has truly positioned itself as a leader in the antibody drug conjugate and precision biologics space, working together with our partners, demonstrating promising data from its ongoing trials. I look forward to furthering our clinical development throughout 2022, bringing value to stakeholders and patients alike."

2H 2021 and Subsequent Clinical Highlights

ARX788 Included in Quantum Leap’s I-SPY 2.2 Phase 2 Clinical Trial in Breast Cancer. In April 2022, Ambrx announced the inclusion of ARX788 in Quantum Leap Healthcare Collaborative’s I-SPY 2.2 Phase 2 clinical trials in patients with HER2-positive breast cancer. ARX788 will be evaluated as a monotherapy and in combination with cemiplimab, in HER2-positive early-stage breast cancer in the neoadjuvant setting.
Acceptance of an Investigational New Drug Application (IND) for ARX305 to the U.S. Food and Drug Administration (FDA). In February 2022, Ambrx announced that the FDA had accepted the company’s IND for ARX305 for the treatment of solid and hematological tumors and provided a "Study May Proceed" letter. The acceptance allows Ambrx to prepare a first in human, Phase 1 clinical trial of ARX305.
Positive Data on ARX788 for the Treatment of HER2+ Metastatic Breast Cancer Presented at SABCS. In December 2021, Ambrx presented positive data from the ACE-Breast-01 Phase 1 clinical trial of ARX788 for the treatment of HER+ positive metastatic breast cancer in patients whose disease is resistant/refractory to HER2 targeted agents including trastuzumab, ADCs, TKIs (tyrosine kinase inhibitors) and bispecific antibodies. At 1.5 mg/kg every three weeks, ARX788 demonstrated robust treatment effect with a disease control rate of 100% in 29 evaluable patients.
First Patient Dosed in Phase 2 ACE-Breast-03 Clinical Trial of ARX788. In November 2021, the company announced that the first patient had been dosed in its global ACE-Breast-03 Phase 2 clinical trial of ARX788 in patients with HER2+ metastatic breast cancer. The Phase 2 trial will measure the objective response rate in patients whose HER2+ metastatic breast cancer is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regiments.
Positive Data on ARX788 for the Treatment of HER2+ Gastric Cancer Presented at CSCO. In October 2021, NovoCodex Pharmaceuticals Ltd., Ambrx’s partner in China, presented positive interim data from the ACE-Gastric-01 Phase 1 clinical trial of ARX788 for the treatment of HER2+ metastatic gastric / gastroesophageal junction (GEJ) cancer.
First Patient Dosed in a Phase 1 Trial for ARX517. In August 2021, Ambrx announced that the first patient had been dosed in a Phase 1, multicenter, dose-escalation, and dose expansion trial to evaluate the safety, pharmacokinetics, and anti-tumor activity of ARX517, an ADC being developed to treat subjects with prostate specific membrane antigen (PSMA) expressing tumors.
2H 2021 and Subsequent Corporate Highlights

Strengthened Board of Directors. In February 2022, Ambrx appointed Paul Maier to its Board of Directors and as Chair of the Audit Committee. Mr. Maier joins Ambrx’s Board with more than 25 years in senior operational, international and financial management experience in rapid growth biotechnology companies.
Anticipated Near-Term Milestones

Topline Phase 3 data in ACE-Breast-02 by the end of 2022
Additional Phase 1 data in ACE-Pan Tumor-01 in 2H 2022
Interim Phase 1 safety data in ARX517 for PSMA in 2H 2022
Initiate Phase 1 trial in ARX305 for RCC and other cancers in 2H 2022
Submit IND to FDA for ARX102 in 2H 2022
Financial Highlights

Cash and Cash Equivalents: Cash and cash equivalents were $170.1 million as of December 31, 2021, compared to $167.2 million for the first half ended June 30, 2021.
Revenue: Revenue was $2.4 million and $7.5 million for the six months and full year ended December 31, 2021, respectively, as compared to $7.2 million and $13.7 million for the six months and full year ended December 31, 2020, respectively. The decrease was primarily driven by less revenue recognized in connection with our R&D and license agreements including a cumulative catch-up adjustment, partially offset by increased third party reimbursable charges.
Research and development (R&D) expenses: R&D expenses were $32.7 million and $54.8 million for the six months and full year ended December 31, 2021, respectively, as compared to $10.5 million and $20.4 million for the six months and full year ended December 31, 2020, respectively. The increase year over year of $34.4 million was mainly due to increased costs related to clinical trial program spend primarily driven by our ARX788 clinical trials and related manufacturing and outside services costs as well as personnel related costs including stock-based compensation expense.
General and administrative (G&A) expenses: G&A expenses were $8.7 million and $17.1 million for the six months and full year ended December 31, 2021, respectively, as compared to $3.8 million and $6.4 million for the six months and full year ended December 31, 2020, respectively. The increase year over year of $10.7 million was mainly attributable to professional services and fees in connection with preparing for Ambrx’s IPO and operating as a public company, expenses associated with the corporate structure reorganization, and personnel related costs including stock-based compensation expense.
Other expenses: Other expense, net, for the six months and full year ended December 31, 2021 was zero and $3.9 million, respectively, as compared to $4.7 million for the six months and full year ended December 31, 2020.
Net loss: Net loss for the six months and full year ended December 31, 2021 was $39.1 million and $68.1 million, respectively, as compared to $11.1 million and $16.5 million for the six months and full year ended December 31, 2020, respectively.

On April 26, 2022 Arcus Biosciences (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported it will report financial results and key pipeline updates for the first quarter ended March 31, 2022 after the U.S. markets close on Monday, May 9, 2022 (Press release, Arcus Biosciences, APR 26, 2022, View Source [SID1234612991]).

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On April 26, 2022 Gilead Sciences, Inc. (Nasdaq: GILD) reported that its executives will be speaking at the following investor conferences (Press release, Gilead Sciences, APR 26, 2022, View Source [SID1234612990]):

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Bank of America Healthcare Conference on Tuesday, May 10 at 5:00pm ET

Bernstein’s Annual Strategic Decisions Conference on Thursday, June 2 at 4:30pm ET

Jefferies Global Healthcare Conference on Wednesday, June 8 at 11:00am ET

Goldman Sachs Global Healthcare Conference on Wednesday, June 15 at 2:20pm ET

The live webcasts can be accessed at the company’s investors page at investors.gilead.com. The replays will be available for at least 30 days following the presentation.