On May 9, 2022 Enlivex Therapeutics Ltd. (Nasdaq: ENLV, the "Company"), a clinical-stage macrophage reprogramming immunotherapy company, reported the poster presentation of a substantial survival benefit of AllocetraTM combined with immune checkpoint inhibition in a preclinical mesothelioma study at the International Society of Cell and Gene Therapy Annual 2022 Meeting (Press release, Enlivex Therapeutics, MAY 9, 2022, View Source [SID1234613905]). The poster was titled, "Allocetra-OTS, an Early Apoptotic Cellular Therapy Synergize with Chimeric Antigen Receptor (CAR) T Cell Therapy or Immune Check Point Inhibitor Against Peritoneal Solid Tumor."

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Mesothelioma, Treatment Landscape, and Macrophage-Solid Tumor Dynamics

Mesothelioma is one of the deadliest solid cancers with few treatment options, all of which have limited efficacy. People who are most at risk to develop mesothelioma generally have had long-term exposure to asbestos (e.g., construction workers, pipe fitters, and shipyard workers). It takes many years for mesothelioma to develop; it can appear 30 years after asbestos exposure. Immune checkpoint inhibitors targeting CTLA4 and PD1 are FDA-approved as first-line treatments for patients with unresectable malignant pleural mesothelioma.

In mesothelioma and in some other solid cancers, tumor cells, as part of their defense mechanisms, facilitate the recruitment of macrophages which become "pro-tumor" tumor associated macrophages (TAMs) rather than "anti-tumor" macrophages. The TAMs typically form a physical layer on top of the solid tumor, and induce immunosuppression in the solid tumor microenvironment. This in-turn promotes tumor growth and metastasis and makes it very difficult for the immune system or any anti-cancer drug to efficiently attack the cancerous cells. Allocetra is a cell therapy in development that is targeted at these TAMs, and its proposed mechanism of action is to change the balance of macrophage populations to skew towards anti-tumor macrophages and away from pro-tumor macrophages.

The Mesothelioma Model

To test the potential effect of cell therapy-induced macrophage reprogramming on difficult-to-treat solid tumors, Enlivex ran preclinical studies in which five groups of mice were implanted with mesothelioma cancer cells. The difference between the groups was the treatment given, which started on day 12 after the cancer’s initial growth period.

Results from multiple studies strongly support the potential of AllocetraTM to assist in the process of macrophage reprogramming in the solid tumor microenvironment and significantly change survival outcomes. As expected, only 1/16 (6%) of the untreated mice remained alive at day 42 (that one last remaining mouse died on day 65), compared with up to 25% survival for the mice in the group that was treated with the anti-CTLA4 immune checkpoint inhibitor. Surprisingly, AllocetraTM as a stand-alone treatment provided comparable survival rates as anti-CTLA4 monotherapy, with a 28.5% survival rate and a delayed cancer growth rate observed. Notably, the synergistic effect of treating with both drugs resulted in up to 100% survival with complete disappearance of the cancer. The effect was correlated with the AllocetraTM treatment dose. A lower dose of AllocetraTM provided slightly lower survival and cancer complete remission rates (67% complete remission for the low-dose treatment vs. up to 100% for the higher dose). The following chart provides a visual guide to the progressions/regression of the mesothelioma cancer in the different groups, as recorded for study mesothelioma AB12 137:

Across multiple studies of the AB12 mesothelioma model, anti-CTLA4 therapy significantly improved survival duration from mean 34±9 to 44.9 ±20 days (p<0.05). Allocetra as a stand-alone therapy improved survival duration to 52.3 ±20 days (p<0.02). The synergistic effect of the combination therapy of anti-CTLA4 + AllocetraTM improved survival duration to 86.7±20 days (p<0.0001) with complete cancer remission in 60-100% of mice, depending on the dose administered.

Prof. Dror Mevorach, Chief Scientific Officer of Enlivex, stated: "This reproducible and statistically significant data strongly support Allocetra’s proposed therapeutic mechanism of action of reprogramming macrophages in solid tumors. We believe that, in contrast to CAR-T, CAR-NK and other anti-cancer cell therapies directed at tumor antigens, AllocetraTM restores macrophage homeostasis in the tumor environment via reprogramming of pro-tumor macrophages. This may ultimately allow immune checkpoint inhibitors to be exponentially more effective."

Oren Hershkovitz, Ph.D., CEO of Enlivex, added: "Based on these results, Enlivex is planning to initiate a series of clinical trials during 2022 that are designed to evaluate Allocetra in combination with FDA-approved immune checkpoint inhibitor therapies in patients with advanced-stage solid tumors. To date, we have infused AllocetraTM in dozens of hospitalized patients in fragile condition resulting from sepsis and COVID-19-related organ dysfunction. We believe that the proposed differentiated mechanism of action of AllocetraTM, together with the safety and tolerability it has demonstrated in these prior studies, as well as the encouraging efficacy results of our preclinical solid tumor models, highlight an intriguing opportunity for Enlivex to provide another layer of life-saving therapy for patients who have few available options."

ABOUT ALLOCETRA

Allocetra is being developed as a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state. Diseases such as solid cancers, sepsis, and many others reprogram macrophages out of their homeostatic state. These non-homeostatic macrophages contribute significantly to the severity of the respective diseases. By restoring macrophage homeostasis, Allocetra has the potential to provide a novel immunotherapeutic mechanism of action for life-threatening clinical indications that are defined as "unmet medical needs", as a stand-alone therapy or in combination with leading therapeutic agents.

On May 9, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the first quarter ended March 31, 2022 (Press release, CRISPR Therapeutics, MAY 9, 2022, View Source [SID1234613921]).

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"I am pleased with the ongoing momentum across our broad portfolio of innovative gene therapy candidates and anticipate important company milestones in 2022. Alongside our partner Vertex, we remain on track to submit global regulatory filings for CTX001 in late 2022 and have dosed more than 75 patients across both trials to date. We have also initiated two new Phase 3 trials of CTX001 in pediatric patients with TDT and SCD," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "We are also advancing our wholly-owned immuno-oncology pipeline, with new updates expected this year. In addition, enrollment and dosing continues in the Phase 1 clinical trial of VCTX210 for T1D with our partner, ViaCyte. We believe we are well positioned and well capitalized to advance our pipeline and platform to develop transformative medicines for patients suffering from serious diseases."

Recent Highlights and Outlook

Beta Thalassemia and Sickle Cell Disease

Following the completion of enrollment in the ongoing Phase 3 clinical trials for CTX001 in transfusion-dependent beta thalassemia (TDT) and severe sickle cell disease (SCD), announced last quarter, more than 75 patients across both trials have been dosed to date. CRISPR Therapeutics and Vertex anticipate presenting updated data from the clinical trials, with more patients and longer follow-up, at medical conferences in 2022.

CRISPR Therapeutics and Vertex have initiated two new Phase 3 studies of CTX001 in pediatric patients with TDT and SCD.

The companies anticipate submitting global regulatory filings for CTX001 in TDT and SCD in late 2022.

Immuno-Oncology Programs

CRISPR Therapeutics continues to enroll and dose patients in the pivotal trial of CTX110, its wholly-owned allogeneic chimeric antigen receptor T cell (CAR-T) investigational therapy targeting CD19+ B-cell malignancies. The Company expects to report additional data in 2022.

CRISPR Therapeutics’ Phase 1 clinical trials for CTX-120, its wholly-owned allogeneic CAR-T investigational therapy targeting B-cell maturation antigen for the treatment of relapsed or refractory multiple myeloma, and CTX130, its wholly-owned allogeneic CAR-T investigational therapy targeting CD70 for the treatment of both solid tumors and certain hematologic malignancies, are ongoing. Each trial is assessing safety and efficacy of several dose levels. The Company expects to provide updates from each trial in the first half of 2022.

Regenerative Medicine and In Vivo Programs

Enrollment and dosing are ongoing in the Phase 1 clinical trial of VCTX210 for the treatment of type 1 diabetes (T1D). VCTX210 is an investigational, allogeneic, gene-edited, stem cell-derived product developed in collaboration by applying CRISPR Therapeutics’ gene-editing technology to ViaCyte’s proprietary stem cell capabilities for the generation of pancreatic cells designed to evade recognition by the immune system. This immune-evasive cell replacement therapy is designed to enable patients to produce their own insulin.

Based upon ongoing progress with its in vivo approaches for liver gene editing utilizing both viral and non-viral delivery vehicles, CRISPR Therapeutics continues to expect to move multiple programs utilizing in vivo approaches into the clinic in the next 18 to 24 months.

Other Corporate Matters

In April, CRISPR Therapeutics proposed to elect Maria Fardis, Ph.D., MBA, to its Board of Directors at the Company’s upcoming annual general meeting of shareholders to be held later this year. The Company believes her extensive leadership in scaling companies and bringing novel therapies to patients will be an invaluable asset to CRISPR Therapeutics.

In April, CRISPR Therapeutics and Nkarta, Inc. presented preclinical data focused on its natural killer cell platform and pipeline at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022. The data shows that CD70/CISH/CBLB triple KO CD70-CAR NK cells demonstrated enhanced anti-tumor activity against relevant solid tumor cell lines and provided greater resistance to tumor microenvironment inhibition. These data support the further exploration of CD70/CISH/CBLB triple gene knockout CD70 CAR NK cells for clinical application.

In April, CRISPR Therapeutics was awarded the 2022 Facility of the Year Category Award (FOYA) for Innovation by the International Society for Pharmaceutical Engineering (ISPE) for its state-of-the art manufacturing facility in Framingham, Massachusetts, USA. ISPE’s Facility of the Year Awards program is the premier global awards program recognizing innovation and creativity in the pharmaceutical and biotechnology manufacturing industries. Projects selected for recognition set the standard by demonstrating excellence in facility design, construction, and operations.
First Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $2,221.3 million as of March 31, 2022, compared to $2,379.1 million as of December 31, 2021. The decrease in cash of $157.8 million was primarily driven by cash used in operating activities to support ongoing research and development of the Company’s clinical and pre-clinical programs.

Revenue: Total collaboration revenue was $0.2 million for the first quarter of 2022 and 2021.

R&D Expenses: R&D expenses were $118.2 million for the first quarter of 2022, compared to $70.6 million for the first quarter of 2021. The increase in expense was driven by development activities supporting the advancement of our wholly-owned immuno-oncology programs, as well as expenses related to our new U.S. research and development headquarters.

G&A Expenses: General and administrative expenses were $28.0 million for the first quarter of 2022, compared to $24.5 million for the first quarter of 2021. The increase in general and administrative expenses was primarily driven by headcount-related expense.

Collaboration Expense: Collaboration expense, net, was $30.6 million for the first quarter of 2022, compared to $19.9 million for the first quarter of 2021. The increase in collaboration expense, net, was primarily driven by increased pre-commercial and manufacturing scale-up costs associated with our hemoglobinopathies programs under our collaboration with Vertex.

Net Loss: Net loss was $179.2 million for the first quarter of 2022, compared to a net loss of $113.2 million for the first quarter of 2021.
About CTX001
CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate or eliminate transfusion requirements for patients with TDT and reduce or eliminate painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published as a Brief Report in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About the CRISPR-Vertex Collaboration
Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development, manufacturing and commercialization of CTX001 and split program costs and profits worldwide 60/40 with CRISPR Therapeutics.

About CLIMB-111
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-131
This is a long-term, open-label trial to evaluate the safety and efficacy of CTX001 in patients who received CTX001 in CLIMB-111 or CLIMB-121. The trial is designed to follow participants for up to 15 years after CTX001 infusion.

About CTX110
CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial. CTX110 has been granted Regenerative Medicine Advanced Therapy designation from the FDA.

About CARBON
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies.

About CTX120
CTX120, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting B-cell maturation antigen, or BCMA. CTX120 is being investigated in an ongoing Phase 1 single-arm, multi-center, open-label clinical trial designed to assess the safety and efficacy of several dose levels of CTX120 for the treatment of relapsed or refractory multiple myeloma. CTX120 has been granted Orphan Drug designation from the FDA.

About CTX130
CTX130, a wholly-owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being developed for the treatment of both solid tumors, such as renal cell carcinoma, and T-cell and B-cell hematologic malignancies. CTX130 is being investigated in two ongoing independent Phase 1, single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 for the treatment of relapsed or refractory renal cell carcinoma and various subtypes of lymphoma, respectively. CTX120 has been granted Orphan Drug designation for the treatment of T-cell lymphoma from the FDA.

About VCTX210
VCTX210 is an investigational, allogeneic, gene-edited, immune-evasive, stem cell-derived therapy for the treatment of type 1 diabetes (T1D). VCTX210 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and ViaCyte, Inc.

On May 9, 2022 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, reported financial results for the first quarter ended March 31, 2022 and provided a business update (Press release, Precision Biosciences, MAY 9, 2022, View Source [SID1234613937]).

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"We continue to focus on execution and build on the utility of ARCUS as a premier genome editing platform to develop novel treatments for cancer and genetic diseases. We believe the differentiated attributes of ARCUS enable a high degree of specificity, minimal levels of off-target editing and maximum versatility, including gene insertion. These qualities underpin our organic strategy and attract accomplished partners that extend our reach to more patients with serious diseases while also providing capital to advance our core development priorities," said Michael Amoroso, Chief Executive Officer at Precision BioSciences. "As our programs continue to mature, we will remain nimble and follow the data to prudently manage our portfolio. This will allow us to hone in on the most impactful approaches to develop potential allogeneic CAR T product candidates and pursue optimal strategies for delivery to various tissues for gene editing in vivo."

"As we look ahead, we plan to provide an update across our allogeneic CAR T programs in June 2022 as data matures. On the research front, we have initiated IND-enabling studies for PBGENE-PH1 delivered by LNP as we target advancing three wholly owned in vivo gene editing programs towards IND or CTA applications over the next three years," Mr. Amoroso continued.

Recent Developments and Upcoming Milestones:

Ex Vivo Allogeneic CAR T Portfolio:

PBCAR0191: PBCAR0191 is the Company’s lead investigational anti-CD19 allogeneic CAR T candidate being evaluated in a Phase 1/2a clinical trial of adult subjects with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL). In December 2021, Precision announced a Phase 1 data update, in which a 100% overall response rate (6/6) and a 66% complete response rate (4/6) was observed among patients that previously received an autologous CAR T therapy and progressed. Precision prioritized enrollment of this high unmet need patient population as a potential path for PBCAR0191, and the Company plans to provide a program update on PBCAR0191 in June 2022.
PBCAR19B: PBCAR19B is a novel, immune-evading stealth cell candidate employing a single-gene edit to knock-down beta-2 microglobulin and insert an HLA-E transgene. We believe PBCAR19B is the first CAR T cell candidate in the clinic designed to evade rejection by host T cells and natural killer (NK) cells. Precision initiated a clinical trial of PBCAR19B in patients with NHL in mid-2021 and plans to commence dosing in the third quarter of 2022 at the next dose level with clinical trial material from an optimized manufacturing process. The Company plans to provide a program update on PBCAR19B in June 2022.
PBCAR269A: PBCAR269A is an investigational allogeneic CAR T cell candidate targeting B-cell maturation antigen (BCMA) for R/R multiple myeloma. Precision is evaluating PBCAR269A in a Phase 1/2a study in combination with nirogacestat, a gamma secretase inhibitor developed by SpringWorks Therapeutics. The first patient was dosed in the combination arm in June 2021, and Precision expects to provide a program update on PBCAR269A in June 2022.
In Vivo Gene Editing Portfolio:

Over the next three years, Precision expects that three of its wholly owned preclinical in vivo programs will advance to IND or CTA. This includes:

PBGENE-PCSK9: In 2021, Precision initiated a collaboration with iECURE, pursuant to which Precision’s PBGENE-PCSK9 candidate is expected to advance through preclinical activities as well as a Phase 1 study in familial hypercholesterolemia. A CTA filing is expected as early as the end of 2022.
PBGENE-PH1: Precision has initiated IND-enabling activities for its PBGENE-PH1 candidate designed to knock out the well-validated HAO1 gene as a potential one-time treatment for primary hyperoxaluria type 1 (PH1). In the first quarter of 2022, the Company initiated a non-human primate study for PBGENE-PH1 delivered by LNP and expects to submit an IND or CTA in 2023.
PBGENE-HBV: Precision’s gene editing program for chronic Hepatitis B applies ARCUS to knock out persistent covalently closed circular DNA (cccDNA) and inactivate integrated hepatitis B genomes, potentially achieving durable HBV S-antigen (HBsAg) loss and viral persistence. Precision plans to pursue clinical development of its PBGENE-HBV candidate using LNP delivery and expects to submit an IND/CTA in 2024.
Precision continues its in vivo gene editing collaboration with Lilly and is applying ARCUS nucleases for three initial targets, including Duchenne muscular dystrophy in muscle, a central nervous system directed target and a liver directed target. In addition, Precision continues to engage discussions with potential biotech collaborators to leverage the unique attributes of ARCUS, such as gene insertion, for a variety of disease targets.

As announced on May 2, 2022, preclinical data on Precision’s wholly owned PH1 and HBV programs will be presented at the upcoming American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) meeting, May 16-19, 2022.

Abstract #239, Optimization of Hydroxyacid Oxidase 1 (HAO1) Targeting ARCUS Nucleases for the Treatment of Primary Hyperoxaluria Type 1
Abstract #447, Targeting the Hepatitis B cccDNA with a Sequence-Specific ARCUS Nuclease to Eliminate Hepatitis B Virus In Vivo
Other Research:

Additional abstracts on ARCUS in vivo gene editing have been accepted for presentation at the upcoming ASGCT (Free ASGCT Whitepaper) meeting, including one abstract on Precision’s mitochondrial DNA preclinical research and one abstract from a research and license collaboration with iECURE and the company’s ornithine transcarbamylase (OTC) deficiency program.

Abstract #561, ARCUS Gene Editing to Eliminate MELAS-associated m.3243A>G Mutant Mitochondrial DNA
Abstract #811, AAV-meganuclease-mediated Gene Targeting Achieves Efficient and Sustained Transduction in Newborn and Infant Macaque Liver
Preclinical research led by the Department of Ophthalmology and Visual Sciences at the University of Louisville using ARCUS genome editing platform for autosomal dominant Retinitis Pigmentosa (adRP) was presented at the recent Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting.

Abstract #3710318, Successful Late-stage Disease Treatment of P23H Human RHO (hRHO) Using ARCUS Nuclease Gene Editing in a Pig Model of Autosomal Dominant Retinitis Pigmentosa (adRP)
Abstract #3712152, Characterization of a Humanized Mouse Model of P23H Rhodopsin Autosomal Dominant Retinitis Pigmentosa (adRP)
Corporate:

Intellectual Property (IP) Update: In March 2022, the U.S. Patent and Trademark Office issued Precision five new U.S. patents further adding to the Company’s IP portfolio that cover the ARCUS platform and its use developing novel ex vivo and in vivo gene editing therapies. The five new patents included: patents relating to methods of using ARCUS nucleases to target sequences in the Hepatitis B virus (U.S. Patent No. 11,274,285); methods for modifying the Factor VIII gene in hemophilia A (U.S. Patent No. 11,278,632); methods for novel co-stimulatory domain used for allogeneic CAR T expansion (U.S. Patent No. 11,286,291); and methods of making allogeneic CAR T cells and T cell receptor alpha chain (TRAC)-targeting ARCUS nucleases useful in such methods (U.S. Patent Nos. 11,268,065 and 11,266,693).
Quarter Ended March 31, 2022 Financial Results:

Cash and Cash Equivalents: As of March 31, 2022, Precision had approximately $116.2 million in cash and cash equivalents. The Company expects that existing cash and cash equivalents, expected operational receipts and available credit will be sufficient to fund its operating expenses and capital expenditure requirements into mid-2023.

Revenues: Total revenues for the quarter ended March 31, 2022 were $3.3 million, as compared to $16.3 million for the same period in 2021. The decrease of $13.0 million in revenue during the quarter ended March 31, 2022 was primarily the result of a $10.3 million decrease in revenue recognized under the Servier Agreement subsequent to full satisfaction of the performance obligation under the execution of the Program Purchase Agreement in April 2021, a $2.1 million decrease in revenue recognized under the Lilly Agreement, and a $0.6 million decrease in revenue recognized from an agriculture partnering collaboration.

Research and Development Expenses: Research and development expenses were $20.0 million for the quarter ended March 31, 2022, as compared to $25.6 million for the same period in 2021. The decrease of $5.6 million was primarily due to decreases of $2.7 million in external development costs, including clinical research organization and clinical manufacturing organization costs, associated with our PBCAR0191, PBCAR269A, PBCAR20A and PBCAR19B clinical trials, as well as decreases of $1.1 million in sublicensing royalty payable to Duke on the Lilly upfront payment that was received in 2021 and $1.4 million in employee-related costs due to reduced headcount driven by the separation of Elo in 2021.

General and Administrative Expenses: General and administrative expenses were $10.7 million for the quarter ended March 31, 2022, as compared to $9.5 million for the same period in 2021. The increase of $1.2 million was primarily due to costs required to meet our growing infrastructure needs, including an increase of $1.3 million in general and administrative employee-related costs associated with increased wages, share-based compensation, relocation and recruiting costs for key management personnel.

Net Loss: Net loss was $28.2 million, or $(0.46) per share (basic and diluted), for the quarter ended March 31, 2022, as compared to a net loss of $18.7 million, or $(0.33) per share (basic and diluted), for the same period in 2021.

On May 9, 2022 Amplia Therapeutics Limited (ASX: ATX) ("Amplia" or the "Company") reported that a pre-Investigational New Drug (pre-IND) interaction with the United States Food and Drug Administration ("FDA") Division of Oncologic Diseases has been conducted (Press release, Amplia Therapeutics, MAY 9, 2022, View Source;[email protected] [SID1234613953]).

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Amplia requested a pre-IND (Type B) meeting to discuss the Company’s proposed development plans for its investigational focal adhesion kinase inhibitor, AMP945, in people with pancreatic cancer. In particular, the Company sought FDA’s feedback on the design of its planned clinical study of AMP945 in first-line patients with advanced pancreatic cancer which is scheduled to commence recruitment in the current calendar quarter.

The FDA advised Amplia that the design of the trial, including selection of the first-line patient population and the proposed dose-escalation followed by a Simon 2-stage design, is generally acceptable. FDA recommended some further pharmacokinetic sampling to more thoroughly interrogate patient exposures to AMP945, gemcitabine and nab-paclitaxel. These recommendations can be readily applied without delaying the trial and Amplia intends to implement the additional assessments in full. FDA also confirmed Amplia’s understanding that dose selection for the Simon 2-stage expansion phase of the trial should be based on a combined view of safety, efficacy, pharmacokinetics and pharmacodynamics across a wide range of doses.

Overall, the FDA commented that the available and planned pre-clinical data appear to support both the trial and a future marketing application in the proposed indication. Furthermore, FDA reviewed the Company’s proposed drug substance and drug product specifications and advised that these appear reasonable.

Amplia has already secured an Orphan Drug Designation (ODD) from the FDA covering the use of AMP945 in the treatment of patients with pancreatic cancer which grants seven years exclusivity and a waiver of FDA fees.

Amplia’s CEO and Managing Director, Dr John Lambert commented that "We are very pleased to receive FDA’s timely and helpful feedback. This pre-IND advice provides early insight into FDA’s priorities and equips us to address these proactively. It also allows us to enter our planned clinical study reassured that our intent to bring first-line patients into the trial is reasonable and acceptable."

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.

On May 9, 2022 Novavax, Inc. (NASDAQ: NVAX), a biotechnology company dedicated to developing and commercializing next-generation vaccines for serious infectious diseases, reported its financial results and operational highlights for the first quarter ended March 31, 2022 (Press release, Novavax, MAY 9, 2022, View Source [SID1234613970]).

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"Novavax has been successful in launching our protein-based COVID-19 vaccine worldwide and executing on our plans for ongoing label expansions for pediatrics and homologous and heterologous boosting. Reinforced by our first profitable quarter, with $704 million in revenue, we are continuing our robust commercial rollout." said Stanley C. Erck, President and Chief Executive Officer, Novavax. "Importantly, as new variants have emerged, we have progressed our strategy to be ready to address the dynamic environment and continue development beyond COVID-19 with our COVID-19-Influenza Combination vaccine candidate."

First Quarter 2022 and Recent Highlights

Expanded Worldwide Authorizations for COVID-19 Primary and Booster Vaccination in Adult Population Aged 18+

Received manufacturing and marketing approval with our partner Takeda Pharmaceutical Company Limited, in Japan for Nuvaxovid for primary, heterologous and homologous boosting indications
Granted authorization (emergency use, provisional, interim or conditional) for Nuvaxovid in Great Britain, Canada, Australia, Switzerland, Singapore and New Zealand
Received full regulatory approval for Nuvaxovid in South Korea with our partner SK bioscience, becoming the first protein-based vaccine approved in South Korea
Granted emergency use authorization (EUA) for Covovax with our partner the Serum Institute of India Pvt. Ltd. (SII) in Thailand and Bangladesh
Submitted request for EUA to U.S. FDA and, with SII, filed for EUA in South Africa
FDA scheduled Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting for June 7th
Progressed COVID-19 Vaccine Regulatory Pathway for Children Aged 12-17 Years

Granted EUA for adolescents in India with SII for Covovax
Submitted requests for authorization for Nuvaxovid in adolescents to the European Union, Great Britain, Australia and New Zealand
Filed for approval of Nuvaxovid with SK bioscience, for adolescents in South Korea
Additional global submissions planned throughout the second quarter of 2022
COVID-19-Influenza Combination (CIC) Vaccine Candidate Clinical Development

Announced initial results of CIC Phase 1/2 trial, combining NVX-CoV2373 and quadrivalent influenza vaccine candidate
Immune response confirmed in stand-alone influenza vaccine candidate and CIC vaccine candidate with potential path forward for both
Demonstrated combined formulation has potential to reduce total antigen amount by up to 50% overall
Expect to begin CIC Phase 2 trial by the end of 2022
COVID-19 Vaccine Supply and Distribution

Delivered Nuvaxovid globally to European Union, Canada, Australia, Thailand, Singapore and New Zealand and with SK bioscience to South Korea
COVID-19 Vaccine Clinical Development

UK Phase 3 study demonstrated ongoing durability of protection against infection and disease in long term follow-up (median of 101 days)
82.5% efficacy in protection against all COVID-19 infection, as measured by PCR+ or anti-N seroconversion
82.7% overall efficacy against disease
100% efficacy against severe disease
Continued rapid development and assessment of strain change, including Omicron-specific clinical studies with topline readout expected in third quarter of 2022
Evaluating benefit of Omicron-specific (BA.1 and BA.2) or bivalent vaccine compared to current prototype, with first doses expected this month
Progressed South Africa Phase 2 study with ongoing administration in participants to evaluate a three-dose regimen and different dosing schedules in -immunocompromised participants, providing flexibility to national delivery programs
Topline results expected in fourth quarter of 2022
Progressed PREVENT-19 Phase 3 study in adolescents aged 12-17 years
Achieved primary effectiveness endpoint and demonstrated comparability to adult population
Demonstrated 80% overall clinical efficacy and 82% efficacy against Delta variant
Vaccine was generally well-tolerated and safety profile was consistent with previous studies
Initiated booster study to evaluate safety and immunogenicity of a third dose
Continued clinical trials in younger age groups to build on positive pediatric data
Expect to initiate PREVENT-19 Phase 3 trial in younger age groups (5-11 years) by third quarter of 2022
SII generated positive data from Phase 2/3 India study in children ages 2-17 years showing robust immune responses with favorable reactogenicity profiles
Announced participation in Phase 1/2 heterologous booster study sponsored by National Institute of Allergy and Infectious Diseases
Evaluating safety, reactogenicity and immunogenicity of heterologous boosters in approximately 180 individuals aged 18 years or older
Topline results expected later this year and full results in 2023
Announced participation in Phase 3 study in the United Arab Emirates evaluating boost with NVX-CoV2373 in participants who were immunized with an inactive COVID-19 vaccine in individuals aged 18 years or older
Financial Results for the Three Months Ended March 31, 2022

Total revenue for the first quarter of 2022 was $704 million, compared to $447 million for the comparable period in 2021. First quarter of 2022 total revenue includes $605 million of revenue comprised of $586 million of product sales from NVX-CoV2373 based on 31 million doses sold by Novavax and $19 million of royalties and adjuvant sales to our license partners. Grant revenue of $99 million in the first quarter of 2022 compared to $447 million in the prior year resulted from a decrease in funding under our agreements with the U.S. government and with the Coalition for Epidemic Preparedness Innovations.
Cost of sales for the first quarter of 2022 were $15 million and 3% of product sales in the period. During 2021 and prior to receipt of regulatory authorizations for NVX-CoV2373, certain manufacturing costs were expensed to research and development that would otherwise have been capitalized to inventory.
Research and development expenses for the first quarter of 2022 were $383 million compared to $593 million for the comparable period in 2021. The decrease was primarily the result of lower clinical development activities for NVX-CoV2373 and the capitalization of NVX-CoV2373 manufacturing costs during the first quarter of 2022.
Selling, general and administrative expenses for the first quarter of 2022 were $96 million compared to $63 million for the comparable period in 2021. The increase in the period was the result of activities in support of the commercial launch of NVX-CoV2373.
Net income for the first quarter of 2022 was $203 million compared to a net loss of $223 million for the comparable period in 2021.
Cash, cash equivalents, and restricted cash were $1.6 billion as of March 31, 2022, compared to $1.5 billion as of December 31, 2021. Through sales of Novavax common stock pursuant to at-the-market (ATM) offerings during the first quarter of 2022, Novavax raised net proceeds of $179 million.
Financial Guidance

Novavax continues to expect to achieve its full year 2022 total revenue of between $4 and $5 billion. Total revenue reflects all sources, including product sales of Nuvaxovid by Novavax, grants revenue, royalties and other revenue.

Conference Call

Novavax will host its quarterly conference call today at 4:30 p.m. ET. The dial-in numbers for the conference call are (833) 974-2381 (Domestic) or (412) 317-5774 (International). Participants will be prompted to request to join the Novavax, Inc. call. A replay of the conference call will be available starting at 7:30 p.m. ET on May 9, 2022 until 11:59 p.m. ET on May 16, 2022. To access the replay by telephone, dial (877) 344-7529 (Domestic) or (412) 317-0088 (International) and use passcode 9339969.

A webcast of the conference call can also be accessed on the Novavax website at novavax.com/events. A replay of the webcast will be available on the Novavax website until August 9, 2022.

About NVX-CoV2373

NVX-CoV2373 is a protein-based vaccine engineered from the genetic sequence of the first strain of SARS-CoV-2, the virus that causes COVID-19 disease. NVX-CoV2373 was created using Novavax’ recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is formulated with Novavax’ patented saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies. NVX-CoV2373 contains purified protein antigen and can neither replicate, nor can it cause COVID-19.

Novavax’ COVID-19 vaccine is packaged as a ready-to-use liquid formulation in a vial containing ten doses. The vaccination regimen calls for two 0.5 ml doses (5 mcg antigen and 50 mcg Matrix-M adjuvant) given intramuscularly 21 days apart. The vaccine is stored at 2°- 8° Celsius, enabling the use of existing vaccine supply and cold chain channels. Use of the vaccine should be in accordance with official recommendations.

Novavax has established partnerships for the manufacture, commercialization and distribution of NVX-CoV2373 worldwide. Existing authorizations leverage Novavax’ manufacturing partnership with Serum Institute of India (SII), the world’s largest vaccine manufacturer by volume. They will later be supplemented with data from additional manufacturing sites throughout Novavax’ global supply chain.

About Matrix-M Adjuvant

Novavax’ patented saponin-based Matrix-M adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen-presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.

About Novavax’ Influenza Program

Novavax’ influenza vaccine, previously known as NanoFlu, is a quadrivalent recombinant hemagglutinin (HA) protein nanoparticle influenza vaccine produced by Novavax in its SF9 insect cell baculovirus system. The influenza vaccine uses HA amino acid protein sequences that are the same as the recommended wild-type circulating virus HA sequences, and contains Novavax’ patented saponin-based Matrix-M adjuvant. This investigational candidate was evaluated during a controlled phase 3 trial conducted during the 2019-2020 influenza season.