On March 30, 2023 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage drug-development company focused on developing DNA-mediated immunotherapy and next-generation vaccines, reported financial results for the year ended December 31, 2022, and provided an update on its clinical development programs with IMNN-001 (formerly GEN-1), a DNA-based interleukin-12 (IL-12) immunotherapy in Phase 2 clinical development for the treatment of advanced-stage ovarian cancer, and with PLACCINE, a proprietary, multivalent DNA plasmid technology utilizing synthetic, non-viral vaccine delivery vectors being evaluated in preclinical studies for superiority over current generation of nucleic acid vaccines (Press release, IMUNON, MAR 30, 2023, View Source [SID1234629590]).

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Highlights of 2022 and recent weeks include:

Completed enrollment in the Phase 1/2 OVATION 2 Study with IMNN-001 in advanced ovarian cancer.
Phase 1/2 Clinical Study of IMNN-001 in combination with Avastin in advanced ovarian cancer was opened to enrollment in the first quarter of 2023.
Reported compelling results from a non-human primate (NHP) study confirming PLACCINE as a viable modality for the development of the next generation of prophylactic vaccines. PLACCINE is IMUNON’s non-viral, non-device plasmid DNA-based vaccine modality targeting multiple antigens from a single vector.
Signed new research collaborations with The Wistar Institute to develop new vaccine formulations utilizing the Company’s PLACCINE modality for the development of vaccines for infectious diseases, and with Acuitas Therapeutics to evaluate IMUNON’s plasmid DNA with Acuitas’ lipid nanoparticle delivery system.
Made strategic investment in Transomic Technologies to strengthen IMUNON’s development capabilities of the PLACCINE DNA vaccine modality.
Reported cash and cash equivalents of $38.9 million as of December 31, 2022, which is expected to fund operations into 2025.
"I am pleased to report that IMUNON made significant progress during 2022 in advancing our clinical programs in immuno-oncology with IMNN-001, our IL-12 gene-mediated immunotherapy. Earlier in the year we reported data from 46 patients in the experimental arm of our OVATION 2 Phase 1/2 study who had undergone interval debulking surgery, showing an improvement in R0 surgical resection rates and CRS 3 chemotherapy response scores over the 41 patients in the control arm. In September we reached full enrollment of 110 patients in this study and expect to report an additional set of interim, more mature data in the second half of 2023 and topline results by mid-2024," said Dr. Corinne Le Goff, IMUNON’s President and Chief Executive Officer.

"Our PLACCINE modality continues to advance with very promising data. We demonstrated the validity of this proprietary technology in prophylactic vaccines, with impressive proof-of-concept data in a COVID-19 model. We also completed the evaluation of our vaccines in non-human primates. I am pleased to report that the final data are consistent with the earlier data and show excellent immunological response and viral clearance. We demonstrated in a recent mouse study that a single dose of our PLACCINE vaccine without a booster dose produced longer duration of IgG responses and higher T-cell activation than an mRNA vaccine. We are now nine months into a 12-month PLACCINE stability study and have demonstrated continued drug stability at the standard refrigerated temperature of 4⁰C, representing a significant commercial advantage over mRNA-based vaccines," she added. "With the continuing volatility of the public markets, our decision to raise capital earlier this year to strengthen our balance sheet and extend our operating runway into 2025 was well timed. We expect to report several value-creating developments during this period."

Dr. Le Goff continued, "This year we anticipate filing an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for our seasonal COVID-19 booster vaccine. Our objective is to confirm in a Phase 1 clinical study the safety of our PLACCINE modality. In the first half of 2023, we intend to apply for a pre-IND consultation with the FDA to receive guidance on our proposed program prior to submitting the IND.

"We also will select our next pathogen target for our PLACCINE modality. It is likely that we will choose a pathogen among the list of priority pathogens established by the Coalition for Epidemic Preparedness Innovations. Our vaccine program objective is to establish the safety and efficacy of our platform in a Phase 1 human study, and then seek to out-license this powerful technology to pharmaceutical companies for the utilization of our platform and/or to establish non-dilutive partnerships to develop vaccines for pathogens of interest."

"We have developed in-house pilot manufacturing capabilities for DNA plasmids and nanoparticle delivery systems. Our scientists can select any protein from the human or pathogen proteomes to be engineered. In combination, during recent months we made an investment in Transomic Technologies, which offers a comprehensive array of CRISPR, RNAi and gene expression tools and services. Our existing labs also have the ability to conduct testing and to run experiments in a variety of animal disease models. These capabilities are expected to allow us to realize our goal of attracting corporate partners while minimizing dependence on vendors so that we control both the costs and the development timelines. Our progress to date is evidence that IMUNON is a fully integrated clinical development company with expertise in running global mid-stage clinical programs," Dr. Le Goff concluded.

RECENT DEVELOPMENTS

PLACCINE: Developing the Prophylactic Vaccines of the Future

Presentation at Vaccine Technology Summit 2023 Describes Compelling Preclinical Data Supporting Continued development of PLACCINE as a Differentiated, Next-Generation Vaccine. In March 2023, Khursheed Anwer, Ph.D., the Company’s Executive Vice President and Chief Science Officer, presented data on the company’s PLACCINE platform at the Vaccine Technology Summit 2023 in Boston. Dr. Anwer’s presentation is titled "A Novel DNA Vaccine Platform with Potential to Create Next Generation Vaccines," and can be found on the company’s website here.

Dr. Anwer reviewed the Company’s work in advancing its PLACCINE modality and the promising preclinical data generated to date. Among topics presented was the ability of this multi-valent technology to achieve broad spectrum immunity from a single DNA plasmid with a synthetic delivery system. This ability is independent of virus, device or liquid nanoparticle formulations. The data presented showed:

Robust immunogenicity and protection in SARS-CoV-2 models
Durable cellular or humoral responses detectable for more than 12 months
Comparable protection activity to a commercial mRNA vaccine in a booster-dose comparison
Superior immune quality versus the mRNA vaccine in a single-dose comparison
In addition, the PLACCINE modality had important distinguishing advantages for a commercial vaccine, including a shelf-life at 4⁰C for greater than nine months, and the ability for simple, rapid and scalable manufacturing.

Presentation at World Vaccine & Immunotherapy Congress Highlights PLACCINE Preclinical Proof of Concept and Key Competitive Advantages. In December 2022, Khursheed Anwer, Ph.D., the Company’s Chief Science Officer, presented at the World Vaccine & Immunotherapy Congress. Dr. Anwer highlighted the PLACCINE modality and proof-of-concept rodent and non-human primate data in SARS-CoV-2. Slides from Dr. Anwer’s presentation are available here.

Final Results from NHP Study and Additional Preclinical Studies Support PLACCINE as a Viable Prophylactic Vaccine Development Modality. In October 2022 the Company reported partial results from an ongoing NHP study designed to examine the immunogenicity of its proprietary DNA-based vaccine in support of PLACCINE as a viable alternative to commercial mRNA vaccines. The study examined a single plasmid DNA vector containing the SARS-CoV-2 Alpha variant spike antigen formulated with a synthetic DNA delivery system and administered by intramuscular injection.

In the study, cynomolgus monkeys were vaccinated with the PLACCINE vaccine or a commercial mRNA vaccine on Day 1, 28 and 84. Analysis of blood samples for IgG and neutralizing antibodies showed evidence of immunogenicity both in PLACCINE and mRNA vaccinated subjects. Analysis of bronchoalveolar lavage for viral load by quantitative PCR showed viral clearance by more than 90% of the non-vaccinated controls. Viral clearance from nasal swab followed a similar pattern in a majority of vaccinated animals and a similar clearance profile was observed when viral load was analyzed by the tissue culture infectious dose method. In a head-to-head comparison, the protection efficiency as measured by viral clearance following challenge with the SARS-CoV-2 virus was similar between PLACCINE and a commercial mRNA vaccine.

On March 1, 2023, IMUNON’s CEO issued a Letter to Shareholders announcing the final results from the Company’s evaluation of its vaccines in NHP. Dr. Le Goff reported that the final data are consistent with the earlier data and show excellent immunological response and viral clearance. The Company reported results from a recent mouse study that demonstrated a single dose of PLACCINE vaccine without a booster dose produced longer duration of IgG responses and higher T-cell activation than an mRNA vaccine as well as nine-month data from a 12-month PLACCINE stability study that demonstrates continued drug stability at 4⁰C (standard refrigerated temperature), representing a significant commercial advantage over mRNA-based vaccines.

IMNN-001 Immunotherapy

Phase 1/2 Clinical Study of IMNN-001 in Combination with Bevacizumab in Advanced Ovarian Cancer was opened to enrollment. In February 2023 the Company announced a collaboration to evaluate IMNN-001 in a Phase 1/2 clinical trial in combination with bevacizumab in ovarian cancer in the frontline, neoadjuvant setting. Working with four of the foremost comprehensive cancer centers in the world, the goal of this project is to transform the care of women with ovarian cancer by developing unprecedented capabilities for understanding and targeting persistent minimal residual disease (MRD), as explained here.

The trial is open to enrollment at the University of Texas MD Anderson Cancer Center with expected additional participation at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and Memorial Sloan Kettering Cancer Center. The Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology will provide artificial intelligence services throughout the trial, including biomarker and genomic analyses, which is expected to expand the Company’s knowledge of the treatment paradigm.

This new Phase 1/2 study, titled "A Phase I/II Study Evaluating the Effect of IMNN-001 (IL-12 Plasmid Formulated with PEG-PEI-Cholesterol Lipopolymer) on Minimal Residual Disease (MRD) as determined by Second Look Laparoscopy when Administered in Combination with Bevacizumab and Neoadjuvant Chemotherapy in Subjects Newly Diagnosed with Advanced Ovarian, Fallopian Tube or Primary Peritoneal Cancer," is expected to enroll 50 patients with Stage III/IV advanced ovarian cancer and is being led by principal investigator Amir Jazaeri, M.D., Professor of Gynecologic Oncology and Reproductive Medicine at MD Anderson. The study will be partially funded by a third party.

Partnerships and Collaborations

Collaborative Research Agreement with The Wistar Institute’s Vaccine & Immunotherapy Center, Acuitas Therapeutics and Transomic Technology. In January 2023 the Company announced a collaborative research agreement with The Wistar Institute, a global leader in biomedical research, through its Vaccine & Immunotherapy Center, to research and develop new vaccine formulations utilizing the Company’s PLACCINE modality for the development of vaccines for infectious diseases. The Wistar Institute Vaccine & Immunotherapy Center possesses world-renowned expertise in cancer, immunology, infectious diseases and vaccine creation. They are uniquely positioned to advance new vaccine formulations and will facilitate further expansion and development of PLACCINE with the goal of expanding vaccine targets ideally matched for the Company’s novel formulated DNA delivery platform.

During the fourth quarter of 2022 the Company entered into an agreement with Acuitas Therapeutics to evaluate PLACCINE Plasmid DNA with Acuitas’ lipid nanoparticle delivery system. Under this agreement, Acuitas will evaluate the administration of IMUNON’s vector constructs formulated in various LNP formulations for gene expression and immunogenicity in murine models. The Company also announced a strategic investment in Transomic Technology to utilize its custom vector construction services to continue to generate plasmids that are being developed and evaluated by IMUNON as part of the Company’s DNA vaccine program. As a condition of the investment, Michael H. Tardugno, IMUNON’s executive chairman, has joined the Transomic board of directors.

Corporate Developments

Received $1.6 Million in Non-Dilutive Funding from the Sale of New Jersey Net Operating Losses. In January 2023, the Company announced it received $1.6 million in net cash proceeds from the sale of approximately $1.7 million of its unused New Jersey net operating losses (NOLs). The NOL sales cover the tax year 2021 and are administered through the New Jersey Economic Development Authority’s (NJEDA) Technology Business Tax Certificate Transfer (NOL) program. This non-dilutive funding further strengthened the Company’s balance sheet. The Company plans to sell an additional $1.9 million of unused New Jersey NOLs available to the Company under the program in 2023.

Financial Results for the Year Ended December 31, 2022

IMUNON reported a net loss for 2022 of $35.9 million, or $5.03 per share, compared with a net loss for 2021 of $20.8 million, or $3.83 per share. Operating expenses were $25.4 million for 2022, an increase of $3.9 million or 18% from $21.5 million for 2021. The Company recognized tax benefits from the sale of its New Jersey NOLs of $1.6 million and $1.4 million in tax in 2022 and 2021, respectively.

Research and development (R&D) expenses were $11.7 million for 2022, an increase of $1.1 million from $10.6 million for 2021. Costs associated with the OVATION 2 Study were $1.5 and $1.3 million for 2022 and 2021, respectively. Costs associated with the Phase 3 OPTIMA Study decreased to $0.5 million for 2022, compared with $1.0 million for 2021. Other clinical and regulatory costs were $2.3 million for 2022, compared with $2.6 million for 2021. R&D costs associated with the development of IMNN-001 to support the OVATION 2 Study, as well as development of the PLACCINE DNA vaccine technology platform increased to $6.1 million for 2022, compared with $4.3 million for 2021. CMC costs decreased to $1.2 million for 2022, compared with $1.5 million for 2021 due to the discontinuation of the ThermoDox clinical development program in primary liver cancer.

General and administrative expenses were $13.7 million for 2022, compared with $10.9 million for 2021. This $2.8 million increase was primarily attributable to higher professional fees including legal fees to defend various lawsuits filed after the announcement in July 2020 of the OPTIMA Phase 3 study results, higher compensation expenses related to the CEO succession plan and higher staffing costs, which were partially offset by lower non-cash stock compensation expense.

Other non-operating expenses were $12.5 million for 2022, compared with $1.1 million for 2021. This increase was attributable to the following:

Due to the continuing deterioration of the public capital markets in the biotech industry in 2021 and 2022 and its impact on the market capitalization of companies in this sector, the Company reviewed its In-Process Research & Development (IPR&D) asset for impairment. After conducting a detailed analysis, the Company determined that the IPR&D asset was impaired. As of December 31, 2022, the Company wrote off the $13.4 million carrying value of this asset, thereby recognizing a non-cash charge of $13.4 million.
The Company wrote off the earn-out milestone liability because of the requirements not being achieved and recognized a non-cash gain of $5.4 million during 2022 as a result of the change in the fair value of the earn-out milestone liability.
The Company recognized interest expense of $5.0 million for 2022, compared with $0.6 million for 2021. In June 2021, the Company entered into a $10.0 million loan facility with Silicon Valley Bank (SVB). The Company immediately used $6.0 million from this facility to retire all outstanding indebtedness with Horizon Technology Finance Corporation. In connection with the SVB and Horizon loan facilities, the Company incurred $0.5 million in interest expense in 2022, compared with $0.6 million in 2021. In connection with the termination of the Horizon loan facility in 2021, the Company paid early termination and end-of-term charges to Horizon and recognized $0.2 million as a loss on debt extinguishment.
In 2022 the Company incurred additional interest expense attributable to the one-time payment of $4.5 million in interest and offering expenses resulting from the sale and subsequent redemption of $30.0 million of Series A & B convertible redeemable preferred stock.
Investment income from the Company’s short-term investments was $0.5 million for 2022. Investment income was insignificant for 2021.
Net cash used for operating activities was $23.1 million for 2022, compared with $16.2 million for 2021. This increase was primarily due to the one-time payment of $4.5 million in interest expense resulting from the sale and subsequent redemption of $30.0 million of Series A & B convertible redeemable preferred stock, as well as higher operating costs attributable to the development of IMNN-001 and the PLACCINE DNA technology platform and higher legal and professional fees. Cash provided by financing activities of $6.7 million during 2022 resulted from an at-the-market equity offering with no warrants and sales under the Company’s At-the-Market Equity Facility.

The Company ended 2022 with $38.9 million in cash, investments, accrued interest receivable and restricted cash. Along with future planned sales of the Company’s remaining New Jersey NOLs, the Company believes it has sufficient capital resources to fund its operations into 2025.

Conference Call and Webcast

The Company is hosting a conference call to provide a business update, discuss 2022 financial results and answer questions at 11:00 a.m. Eastern time today. To participate in the call, please dial 866-777-2509 (Toll-Free/North America) or 412-317-5413 (International/Toll), and ask for the IMUNON 2022 Earnings Call. A live webcast of the call will be available here.

The call will be archived for replay until April 13, 2023. The replay can be accessed at 877-344-7529 (U.S. Toll-Free), 855-669-9658 (Canada Toll-Free) or 412-317-0088 (International Toll), using the replay access code 5236742. A webcast of the call will be available here for 90 days.

On March 30, 2023 Fortress Biotech, Inc. (Nasdaq: FBIO) ("Fortress"), an innovative biopharmaceutical company focused on efficiently acquiring, developing and commercializing or monetizing promising therapeutic products and product candidates, reported financial results and recent corporate highlights for the full-year ended December 31, 2022 (Press release, Fortress Biotech, MAR 30, 2023, View Source [SID1234629603]).

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Lindsay A. Rosenwald, M.D., Fortress’ Chairman, President and Chief Executive Officer, said, "In 2022, we continued to advance our extensive portfolio of multiple clinical-stage programs, several of which are late-stage and pivotal. We also generated record consolidated net revenues of $75.7 million, much of which came from the sales of our eight marketed dermatology products. Our growth continues in 2023, as the U.S. Food and Drug Administration ("FDA") accepted for filing the Biologics License Application ("BLA") for cosibelimab earlier this month and we expect to have two New Drug Applications ("NDA") submitted to the FDA for CUTX-101 for Menkes disease and DFD-29 for rosacea this year. We also anticipate multiple clinical trial initiations, data readouts and regulatory filings across our other development-stage programs. Fortress has also established 25 acquisition companies with expert opinion leaders in multiple therapeutic areas over the past year. These expert opinion leaders will continue to work with our business development team to identify, evaluate and acquire potential best-in-class therapies to form the bases of these new companies. We are focused on licensing assets with proof-of-concept clinical data available in areas with high unmet medical need, which potentially lowers the development uncertainty and associated risk. Our pipeline and structure allow for flexibility and diversified exposure with many product candidates and potentially long-term revenue streams. We expect to achieve multiple milestones this year, and we are confident in our long-term growth prospects as we continue to scale."

2022 and Recent Corporate Highlights1:

Marketed Dermatology Products and Product Candidates

● Journey Medical Corporation (Nasdaq: DERM) ("Journey Medical"), our partner company, currently markets eight prescription dermatology products.
● Journey Medical’s total net revenues were $73.7 million for the full-year 2022, which includes $71.0 million from their commercial portfolio, compared to full-year 2021 total net revenues of $63.1 million, representing growth of 17%.
● In January 2023, Journey Medical completed enrollment in its DFD-29 Phase 3 clinical program for the treatment of papulopustular rosacea. Topline data from the two DFD-29 Phase 3 clinical studies are expected to be announced in the first half of 2023. Journey Medical plans to submit the NDA for DFD-29 in the second half of 2023 and an FDA approval decision is anticipated in the second half of 2024.
o

In the Phase 2 clinical trials, DFD-29 (40mg) demonstrated nearly double the efficacy when compared against Oraycea (European equivalent of Oracea) on both co-primary endpoints. For the first co-primary endpoint, Investigator’s Global Assessment ("IGA") treatment success, Oraycea had a 33.33% IGA treatment success rate, while DFD-29 achieved a 66.04% IGA treatment success rate. For the second co-primary endpoint, the change in total inflammatory lesion count, Oraycea had a 10.5 reduction in inflammatory lesions, while DFD-29 achieved a 19.2 reduction in inflammatory lesions.

Cosibelimab (Anti PD-L1 antibody)

● Our partner company, Checkpoint Therapeutics, Inc. (Nasdaq: CKPT) ("Checkpoint"), submitted a BLA to the FDA for cosibelimab, its investigational anti-PD-L1 antibody, as a treatment for patients with metastatic or locally advanced cutaneous squamous cell carcinoma ("cSCC") who are not candidates for curative surgery or radiation, in January 2023. In March 2023, the FDA accepted for filing the BLA for cosibelimab and set a Prescription Drug User Fee Act ("PDUFA") goal date of January 3, 2024. In its BLA filing acceptance letter, the FDA indicated that no potential filing review issues have been identified, and that an advisory committee meeting to discuss the application is not currently planned. According to U.S. prescription claims data, in 2021, approximately 11,000 cSCC patients were treated with systemic therapies. As PD-1 inhibitors comprised less than half of patient prescriptions, cSCC remains a disease with a need for more effective and tolerable treatment options, particularly for the significant number of cSCC patients with immunosuppressive conditions or autoimmune diseases. With its unique mechanism of action and compelling safety profile, we believe cosibelimab, if approved, would be uniquely positioned to provide an important new treatment option for cSCC patients that are currently underserved by available therapies.
● In January 2022, Checkpoint announced positive topline results from its registration-enabling clinical trial evaluating the safety and efficacy of the anti-PD-L1 antibody, cosibelimab, administered as a fixed dose of 800 mg every two weeks in patients with metastatic cSCC. The study met its primary endpoint, with cosibelimab demonstrating a confirmed objective response rate ("ORR") of 47.4% (95% CI: 36.0, 59.1) based on independent central review of 78 patients enrolled in the metastatic cSCC cohort using Response Evaluation Criteria in Solid Tumors version 1.1 criteria.
● In June 2022, we announced that the topline results of Checkpoint’s pivotal trial of cosibelimab in metastatic cSCC were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Data highlights included confirmed ORR by independent central review in the modified intent-to-treat
1 The development programs depicted in this press release include product candidates in development at Fortress, at Fortress’ private subsidiaries (referred to herein as "subsidiaries"), at Fortress’ public subsidiaries (referred to herein as "partner companies") and at entities with whom one of the foregoing parties has a significant business relationship, such as an exclusive license or an ongoing product-related payment obligation (such entities referred to herein as "partners"). The words "we", "us" and "our" may refer to Fortress individually, to one or more of our subsidiaries and/or partner companies, or to all such entities as a group, as dictated by context.

population of 48.7% (95% CI, 37.0-60.4) and 13.2% of patients achieved a complete response in target lesions. Cosibelimab was generally well tolerated with no unexpected safety signals.
● Also in June 2022, we announced positive interim results from Checkpoint’s pivotal trial of cosibelimab in locally advanced cSCC. As of the March 2022 data cutoff, the confirmed ORR by independent central review in 31 patients was 54.8% (95% CI: 36.0, 72.7).
● In July 2022, Checkpoint successfully completed two pre-BLA meetings with the FDA (chemistry, manufacturing and controls ("CMC") and clinical/non-clinical). Based upon favorable interactions with the agency, the January 2023 BLA submission included both the metastatic and locally advanced cSCC indications.
● Cosibelimab was sourced by Fortress and is currently in development at Checkpoint.
Dotinurad (Urate Transporter (URAT1) Inhibitor)

● In May 2022, our subsidiary company Urica Therapeutics, Inc. ("Urica") initiated a Phase 1 clinical trial to evaluate dotinurad in healthy volunteers in the United States. Dotinurad is in development for the treatment of gout. We anticipate topline data from the Phase 1 trial in the first half of 2023 and expect to be in pivotal clinical trials in early 2024.
● Dotinurad (URECE tablet) was approved in Japan in 2020 as a once-daily oral therapy for gout and hyperuricemia. Dotinurad was efficacious and well-tolerated in more than 500 Japanese patients treated for up to 58 weeks in Phase 3 clinical trials. The clinical program supporting approval included over 1,000 patients.
● In October 2022, Urica strengthened its leadership team by appointing Jay D. Kranzler, M.D., Ph.D., as Chairman and Chief Executive Officer, and Vibeke Strand, M.D., MACR, FACP, Adjunct Clinical Professor, Division of Immunology/Rheumatology, Stanford University, to Urica’s Board of Directors.
● In December 2022, Urica expanded its exclusive license agreement with Fuji Yakuhin Co. Ltd. ("Fuji") for the development of dotinurad to include the Middle East and North Africa and Turkey territories. The agreement builds upon the exclusive license agreement between Urica and Fuji previously announced in May 2021 to develop dotinurad in the United States, United Kingdom, European Union and Canada.
● Dotinurad was sourced by Fortress and is currently in development at Urica.
MB-106 (CD20-targeted CAR T Cell Therapy)

● In June 2022, we announced that the FDA granted Orphan Drug Designation to MB-106 for the treatment of Waldenstrom macroglobulinemia ("WM"), a rare type of B-cell non-Hodgkin lymphoma ("B-NHL"). Our partner company Mustang Bio, Inc. (Nasdaq: MBIO) ("Mustang Bio"), which is developing MB-106, plans to treat additional WM patients in the Mustang Bio-sponsored Phase 1 portion of its multicenter trial to potentially support an accelerated Phase 2 strategy for WM.
● In October 2022, we announced that the first patient was treated in Mustang Bio’s multicenter, open-label, non-randomized Phase 1/2 clinical trial evaluating the safety and efficacy of MB-106, for the treatment of relapsed or refractory B-NHL and chronic lymphocytic leukemia ("CLL"). In 2023, Mustang Bio anticipates dose escalation and reporting response data at major medical meetings.
● Additionally, in October 2022, we shared interim data from 28 patients treated in the ongoing Phase 1/2 investigator-sponsored clinical trial at Fred Hutch.
o An ORR of 96% and complete response ("CR") rate of 75% were observed in a wide range of hematologic malignancies including follicular lymphoma, CLL, diffuse large B-cell lymphoma and WM. Twelve patients have experienced CR for more than 12 months (10 ongoing), including four patients with CR for more than two years and the longest patient with CR at 33 months. Six patients with initial partial response at 28 days post-treatment improved to CR and all remain in ongoing CR. All three patients previously treated with CD19 CAR T cell therapy responded to treatment with MB-106.
o A favorable safety profile for MB-106 as an outpatient therapy remains, with no cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome ≥ Grade 3 reported to date on this trial.
● MB-106 continues to generate compelling safety and efficacy data, and the product profile of this autologous CD20-directed CAR T is favorable compared to the approved autologous CD19-directed CAR Ts, which are generating an annualized run rate of $3 billion in net sales, based on reported sales in the third quarter of 2022.
● MB-106 was sourced by Fortress and is currently in development at Mustang Bio.
CUTX-101 (Copper Histidinate for Menkes disease)

● Our subsidiary, Cyprium Therapeutics, Inc. ("Cyprium") has completed two pivotal studies in patients with Menkes disease treated with CUTX-101, copper histidinate (CuHis). In the studies, a 79% reduction in risk of death was observed in patients treated within four weeks of birth compared with an untreated historical control cohort of patients, and median overall survival (OS) was 177.1 for CUTX-101 compared to 16.1 months historical control, with a hazard ratio (HR) of (95% CI) = 0.208 (0.094, 0.463) p<0.0001. A 75% reduction in the risk of death was also observed in patients treated after four weeks of birth compared with untreated historical control subjects and median OS was 62.4 and 17.6 months, respectively; HR (95% CI) = 0.253 (0.119, 0.537); p<0.0001.
● In 2021, our subsidiary Cyprium signed a Development and Asset Purchase Agreement with Sentynl Therapeutics, Inc. ("Sentynl"), a wholly owned subsidiary of Zydus Lifesciences Ltd., for CUTX-101 to treat Menkes disease. Cyprium is responsible for the development of CUTX-101 and Sentynl will be responsible for commercialization of CUTX-101, as well as progressing newborn screening activities.
● In December 2021, Cyprium initiated the rolling submission of an NDA to the FDA for CUTX-101, which is ongoing and expected to be completed in 2023.
● In March 2022, Cyprium announced positive data on CUTX-101 were presented as a "Top-Rated Abstract" and poster at the 2022 American College of Medical Genetics and Genomics Clinical Genetics Meeting. The abstract can be viewed here.
● Cyprium will retain 100% ownership over any FDA priority review voucher that may be issued at NDA approval for CUTX-101.
● CUTX-101 was sourced by Fortress and is currently in development at Cyprium.
CAEL-101 (Light Chain Fibril-reactive Monoclonal Antibody for AL Amyloidosis)

● On October 5, 2021, AstraZeneca plc ("AstraZeneca") acquired Caelum Biosciences, Inc. ("Caelum") for an upfront payment of approximately $150 million paid to Caelum shareholders, of which approximately $56.9 million was paid to Fortress, net of Fortress’ $6.4 million portion of the $15 million, 24-month escrow holdback amount and other miscellaneous transaction expenses. The agreement also provides for additional potential payments to Caelum shareholders totaling up to $350 million, payable upon the achievement of regulatory and commercial milestones. Fortress is eligible to receive 42.4% of all potential milestone payments, which together with the upfront payment, would total up to approximately $212 million.
● There are two ongoing Phase 3 studies of CAEL-101 for AL amyloidosis. (ClinicalTrials.gov identifiers: NCT04512235 and NCT04504825).2
● AstraZeneca has estimated that it expects the FDA to accept its BLA submission for review during calendar year 2024.
● CAEL-101 (anselamimab) was sourced by Fortress and was developed by Caelum (founded by Fortress) until its acquisition by AstraZeneca in October 2021.
2 Information on clinicaltrials.gov does not constitute part of this release.

Triplex (Cytomegalovirus ("CMV") vaccine)

● We expect that the Phase 2 clinical trial of Triplex for adults co-infected with HIV and CMV will complete enrollment in the second half of 2023 with topline data anticipated in 2024. The study aims to show potential reduction in intensity of highly active antiretroviral therapy treatment (HAART) which is used in up to 1.7 million treated HIV patients.
● In August 2022, we announced that Triplex received a grant from the National Institute of Allergy and Infectious Diseases that could provide over $20 million in non-dilutive funding. This will fund a 420 patient multi-center, placebo-controlled, randomized Phase 2 study of Triplex for control of CMV in patients undergoing liver transplantation and is expected to begin enrollment this year. The company believes this data set could ultimately be used to support approval of Triplex in this setting.
● Triplex is currently the subject of four clinical trials including: adults undergoing stem cell transplant; adults co-infected with CMV and HIV; and in combination with a CAR T cell therapy for adults with NHL.
● Triplex was sourced by Fortress and is currently in development at our subsidiary company, Helocyte, Inc.
AJ201

● In March 2023, we announced that our partner company, Avenue Therapeutics, Inc. (Nasdaq: ATXI) ("Avenue"), entered into an exclusive license agreement with AnnJi Pharmaceutical Co., Ltd. for intellectual property related to AJ201, a first-in-class clinical asset currently in a Phase 1b/2a study in the U.S. for the treatment of spinal and bulbar muscular atrophy ("SBMA"), also known as Kennedy’s Disease. Kennedy’s Disease is a debilitating rare genetic neuromuscular disease primarily affecting men. Although there is a range of cited prevalence rates in the literature, a recent study used genetic analysis to estimate disease prevalence of 1:6,887 males3.
● AJ201 was sourced by Fortress and is currently in development at Avenue.
IV Tramadol

● In September 2022, our partner company Avenue received the official meeting minutes from the FDA regarding a meeting conducted in August 2022, for IV Tramadol. At the meeting, Avenue presented a study design for a single safety clinical trial that Avenue believes could address the concerns regarding risks related to opioid stacking. The FDA stated that the proposed study design appears reasonable and agreed on various study design aspects with the expectation that additional feedback would be provided to Avenue upon review of a more detailed study protocol. Avenue incorporated the FDA’s suggestions from the meeting minutes and submitted a detailed study protocol that could form the basis for the submission of a complete response to the second Complete Response Letter for IV Tramadol.
● In March 2023, Avenue participated in a Type C meeting with the FDA to discuss the proposed study protocol to assess the risk of respiratory depression related to opioid stacking on IV Tramadol relative to an approved opioid analgesic.
● IV Tramadol was sourced by Fortress and is currently in development at Avenue.
In vivo CAR T Platform Technology

● We continue to collaborate with the Mayo Clinic to potentially revolutionize the delivery of CAR T in patients. The technology has the potential to generate CAR T cells within the patient’s body after two outpatient injections, without the need for traditional ex vivo allogeneic or autologous CAR T cell processing wait time and expense.
● We anticipate the publication of proof-of-concept research from in vivo animal studies in 2023.
3 M. Zanovello et al., Unexpected frequency of the pathogenic ARCAG repeat 2 expansion in the general population. Brain, in press (2023).

● The novel CAR T technology was sourced by Fortress and is currently in development at Mustang Bio.
General Corporate:

Fortress

● In April 2022, Fortress participated in a two-day summit hosted by the B. Riley Securities’ Healthcare Equity Research team that featured multiple programs from Fortress’ diversified pipeline. Webcast replays are available on Fortress’ website here. Information on our website does not constitute part of this press release.
● In July 2022, we announced that David Jin, who has served as Vice President of Corporate Development since May 2020, was also appointed as Chief Financial Officer effective August 16, 2022.
● In December 2022, Fortress appointed Lucy Lu to its Board of Directors.
● In February 2023, Fortress completed a registered direct offering priced At-the-Market under Nasdaq rules for total gross proceeds of approximately $13.9 million, and a concurrent private placement with investors in the registered direct offering for the pro rata rights to acquire, in the aggregate, securities exercisable into common stock in certain future operating subsidiaries that consummate a specified corporate development transaction within the next five years.
Financial Results:

To assist our stockholders in understanding our company, we have prepared non-GAAP financial metrics for the three months and 12 months ended December 31, 2022 and 2021. These metrics exclude the operations of our four public partner companies: Avenue, Checkpoint, Journey Medical and Mustang Bio, as well as any one-time, non-recurring, non-cash transactions. The goal in providing these non-GAAP financial metrics is to highlight the financial results of Fortress’ core operations, which are comprised of our privately held development-stage entities, as well as our business development and finance functions.

● As of December 31, 2022, Fortress’ consolidated cash, cash equivalents and restricted cash totaled $181.0 million, compared to $210.6 million as of September 30, 2022, and $308.0 million as of December 31, 2021, a decrease of $29.6 million for the fourth quarter and a decrease of $127.0 million for the full year.
● On a GAAP basis, Fortress’ net revenue totaled $75.7 million for the full year ended December 31, 2022, which included $71.0 million in net revenue generated from our marketed dermatology products. This compares to net revenue totaling $68.8 million for the full year ended 2021, which included $63.1 million in net revenue generated from our marketed dermatology products.
● On a GAAP basis, consolidated research and development expenses including license acquisitions totaled $134.9 million for the full year ended December 31, 2022, compared to $128.9 million for the full year ended December 31, 2021. On a non-GAAP basis, research and development costs including research and development license acquisitions totaled $11.3 million for the full year ended December 31, 2022, compared to $18.0 million for the full year ended December 31, 2021.
● On a GAAP basis, consolidated selling, general and administrative costs were $113.7 million for the full year ended December 31, 2022, compared to $86.8 million for the full year ended December 31, 2021. On a non-GAAP basis, selling, general and administrative expenses were $30.6 million for the full year ended December 31, 2022, compared to $28.6 for the full year ended December 31, 2021.
● On a GAAP basis, consolidated net loss attributable to common stockholders was $(86.6) million, or $(0.97) per share, for the full year ended December 31, 2022, compared to net loss attributable to common stockholders of $(64.7) million, or $(0.79) per share for the full year ended December 31, 2021.
● Fortress’ non-GAAP loss attributable to common stockholders was $(29.2) million, or $(0.33) per share, for the full year ended December 31, 2022, compared to Fortress’ non-GAAP income attributable to common stockholders of $25.5 million, or $0.31 per share basic and $0.25 per share
diluted, for the full year ended December 31, 2021. In 2021, Fortress received initial proceeds from the AstraZeneca acquisition of Caelum.
Use of Non-GAAP Measures:

In addition to the GAAP financial measures as presented in our filings with the Securities and Exchange Commission ("SEC"), including our Form 10-K to be filed on March 31, 2023, the Company, in this press release, has included certain non-GAAP measurements. The non-GAAP net loss attributable to common stockholders is defined by the Company as GAAP net loss attributable to common stockholders, less net losses attributable to common stockholders from our public partner companies Avenue, Checkpoint, Journey Medical and Mustang Bio ("public partner companies"), as well as our former subsidiary, Caelum. In addition, the Company has also provided a Fortress non-GAAP loss attributable to common stockholders which is a modified EBITDA calculation that starts with the non-GAAP loss attributable to common stockholders and removes stock-based compensation expense, non-cash interest expense, amortization of licenses and debt discount, changes in fair values of investment, changes in fair value of derivative liability, and depreciation expense. The Company also provides non-GAAP research and development costs, defined as GAAP research and development costs, less research and development costs of our public partner companies and non-GAAP selling, general and administrative costs, defined as GAAP selling, general and administrative costs, less selling, general and administrative costs of our public partner companies.

Management believes each of these non-GAAP measures provide meaningful supplemental information regarding the Company’s performance because (i) it allows for greater transparency with respect to key measures used by management in its financial and operational decision-making; (ii) it excludes the impact of non-cash or, when specified, non-recurring items that are not directly attributable to the Company’s core operating performance and that may obscure trends in the Company’s core operating performance; and (iii) it is used by institutional investors and the analyst community to help analyze the Company’s standalone results separate from the results of its public partner companies. However, non-GAAP loss attributable to common stockholders and any other non-GAAP financial measures should be considered as a supplement to, and not as a substitute for, or superior to, the corresponding measures calculated in accordance with GAAP. Further, non-GAAP financial measures used by the Company and the manner in which they are calculated may differ from the non-GAAP financial measures or the calculations of the same non-GAAP financial measures used by other companies, including the Company’s competitors.

The tables below provide a reconciliation from GAAP to non-GAAP measures:

For the year ended December 31,

($ in thousands except for share and per share amounts)

2022

2021

Net loss attributable to common stockholders

$

(86,575)

$

(64,703)

Net loss attributable to common stockholders – Avenue1

(587)

(822)

Net loss attributable to common stockholders – Checkpoint2

(11,415)

(9,313)

Net loss attributable to common stockholders – Journey Medical3

(17,107)

(36,708)

Net loss attributable to common stockholders – Mustang Bio4

(13,680)

(11,256)

Non-GAAP (loss) attributable to common stockholders

$

(43,786)

$

(6,605)

Stock based compensation

12,706

10,133

Amortization of debt discount

1,532

3,914

Depreciation

385

462

Increase in fair value of investment in Caelum

—

(39,294)

Realization in Caelum investment5

—

56,860

Fortress non-GAAP (loss) income attributable to common stockholders

$

(29,163)

$

25,469

Per common share – basic and diluted:

Net loss attributable to common stockholders (GAAP)

$

(0.97)

$

(0.79)

Non-GAAP net loss attributable to common stockholders

$

(0.49)

$

(0.08)

Fortress non-GAAP (loss) income attributable to common stockholders

$

(0.33)

$

0.31

Fortress non-GAAP (loss) income attributable to common stockholders – diluted

$

(0.33)

$

0.25

Weighted average common shares outstanding – basic

88,874,519

81,700,220

Weighted average common shares outstanding – diluted

88,874,519

103,604,466

1. Avenue net loss for the year ended December 31, 2022 of $3.6 million net of non-controlling interest of $2.4 million, Master Services Agreement ("MSA") fee to Fortress of $0.1 million, financing fee and payment-in-kind ("PIK") dividend to Fortress of $0.3 million and $0.3 million, respectively; net loss for the year ended December 31, 2021 of $3.7 million, net of non-controlling interest of $2.9 million.
2. Checkpoint net loss of $62.6 million net of NCI of $48.4 million, MSA fee to Fortress of $0.5 million, financing fee and PIK dividend to Fortress of $0.4 million and $1.9 million, respectively, for the year ended December 31, 2022; and net loss of $56.7 million net of NCI of $39.2 million, MSA fee to Fortress of $0.5 million, financing fee and PIK dividend to Fortress of $1.0 million and $6.6 million, respectively, for the year ended December 31, 2021.
3. Journey Medical net loss for the year ended December 31, 2022 of $29.6 million net of NCI of $12.5 million and tax expense recognized on a stand-alone basis of $0.1 million; and net loss for the year ended December 31, 2021 of $44.0 million net of NCI of $5.7 million and tax expense recognized on a stand-alone basis of $1.6 million.
4. Mustang net loss of $77.5 million net of NCI of $60.8 million, Fortress MSA fee of $1.0 million, and Fortress financing fee and PIK dividend of $0.9 million and $1.1 million, respectively, for the year ended December 31, 2022; and net loss of $66.4 million net of NCI of $48.5 million, MSA fee to Fortress of $0.5 million and financing fee and PIK dividend to Fortress of $1.9 million and $4.2 million, respectively, for the year ended December 31, 2021.
5. Proceeds received from AstraZeneca plc acquisition of Caelum Biosciences, Inc. in October 2021.

Reconciliation to non-GAAP research and development costs and non-GAAP selling, general and administrative costs

For the year ended December 31,

($ in thousands)

2022

2021

Research and development1

$

134,877

$

128,864

Less:

Research and development – Avenue2

2,388

1,254

Research and development – Checkpoint3

47,940

41,855

Research and development – Journey Medical

10,943

16,558

Research and development – Mustang Bio4

62,340

51,244

Non-GAAP research and development costs

$

11,266

$

17,953

Selling, general and administrative5

$

113,656

$

96,384

Less

General and administrative – Avenue6

5,045

2,484

General and administrative – Checkpoint7

7,782

7,005

Selling, general and administrative – Journey Medical

59,468

49,373

General and administrative – Mustang Bio8

10,795

8,883

Non-GAAP selling, general and administrative costs

$

30,566

$

28,639

1. Includes Research and development expense and Research and development – licenses acquired expense for the periods presented.
2. Excludes $42,000 of Fortress MSA expense and $0.3 million PIK dividend payable to Fortress for the year ended December 31, 2022.
3. Excludes $1.9 million and $6.6 million of PIK dividend payable to Fortress for the year ended December 31, 2022 and 2021, respectively.
4. Excludes $0.5 million of Fortress MSA expense and $1.1 million PIK dividend payable to Fortress for the year ended December 31, 2022; and excludes $0.3 million of Fortress MSA expense and $4.2 million PIK dividend payable to Fortress for the year ended December 31, 2021.
5. Includes Selling, general and administrative expenses and wire transfer fraud loss for the year ended December 31, 2021.
6. Excludes $42,000 of Fortress MSA expense and $0.3 million of Fortress financing fee for the year ended December 31, 2022.
7. Excludes $0.5 million of Fortress MSA expense and $0.4 million Fortress financing fee for the year ended December 31, 2022; and $0.5 million of Fortress MSA expense and $1.0 million Fortress financing fee for the year ended December 31, 2021.
8. Excludes $0.5 million of Fortress MSA expense and $0.9 million Fortress financing fee for the year ended December 31, 2022; and $0.3 million of Fortress MSA expense and $1.9 million Fortress financing fee for the year ended December 31, 2021.

On March 30, 2023 Ensysce Biosciences, Inc. ("Ensysce" or the "Company") (NASDAQ:ENSC), a clinical-stage biotech company applying transformative chemistry to improve prescription drug safety, reported financial results for the fourth quarter and full year of 2022 (Press release, Ensysce Biosciences, MAR 30, 2023, View Source [SID1234629602]).

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Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce, commented, "Our focus remains on execution and advancing clinical development plans for our programs that provide strong pain relief using our PF614 and PF614-MPAR drug products. This has been evident in the recently released news regarding completion of enrollment of our first PF614-MPAR study and completion of the clinical stage of two human abuse potential studies for PF614. These studies add to the clinical support demonstrating that Ensysce has a novel approach for delivering effective pain management and safely alleviating severe pain in patients requiring an opioid analgesic. These recent accomplishments move us closer to our Phase 3 plans and toward bringing what we believe is the ‘Next Generation of Analgesia’ for severe pain to commercialization."

TAAPTM (Opioid Abuse Deterrent Program) Updates

Our lead program, PF614 is a "Trypsin-Activated Abuse Protection" (TAAPTM) extended-release oxycodone. The Company’s TAAPTM technology is designed to control release, be highly resistant to tampering, and reduce abuse through a unique chemical modification that is activated by trypsin. The achievements highlighted below advance the company toward Phase 3 clinical evaluation.

On February 28, 2023, the Company announced the database lock for the oral Human Abuse Potential (HAP) study of PF614. With the database lock, no further change to the trial data is permissible.
On January 4, 2023, the Company announced that it had successfully completed the clinical portion of study PF614-104, ‘A Randomized, Double-Blind, Placebo- and Active-Controlled, Crossover Study to Evaluate the Oral Abuse Potential of PF614 Compared with Oxycodone Immediate-Release Tablets, and Placebo in Non-Dependent Recreational Opioid Users’ (ClinicalTrials.gov: NCT05571345) conducted by Dr. Vince Clinical Research.
On November 14, 2022, the Company announced that it received written guidance from the FDA that an acute pain indication may be appropriate for the Company’s lead Trypsin Activated Abuse Protection (TAAPTM) product, PF614.
On October 31, 2022, the Company announced positive topline results from an intranasal human abuse potential (HAP) study for PF614 showing inhalation of PF614 did not produce the ‘drug liking’ effects of crushed oxycodone. Ensysce’s TAAPTM technology is designed to limit activation to oral administration, be highly resistant to tampering to reduce abuse.
MPARTM (Opioid Abuse Deterrent and Overdose Protection Program) Updates

PF614-MPAR is a combination abuse-protected product designed to overcome prescription drug overdose. MPAR (Multi-Pill Abuse Resistance) reduces the release of the opioid in an overdose situation, providing the additional layer of protection to Ensysce’s TAAP pain medications. The select achievements outlined below demonstrate how Ensysce has progressed, what we believe is the first prescription drug overdose protection technology to be developed.

On March 22, 2023, the Company announced the completion of enrollment in the final stage of the Phase 1 study, PF614-MPAR-101. This study was conducted by Dr. Maria Bermudez MD, at Quotient Sciences, Miami, Florida.
On December 19, 2022, the Company announced data from the initial stage of PF614-MPAR-101 successfully demonstrating the overdose protection qualities of its drug product, PF614-MPAR.
On December 5, 2022, the Company announced that it had completed the clinical portion of the initial stage of PF614-MPAR-101, entitled ‘Single-Dose Study to Evaluate the Pharmacokinetics of oxycodone and PF614, when PF614 Solution is Co-Administered with Nafamostat, as an Immediate-Release Solution and/or Extended-Release (ER) Capsule Formulations in Healthy Subjects’, conducted by Dr. Maria Bermudez MD, at Quotient Sciences, Miami, Florida.
Financial Results

Cash – Cash and cash equivalents were $3.1 million as of December 31, 2022, as compared to $4.5 million as of September 30, 2022, and $12.3 million as of December 31, 2021. Subsequent to year-end, the Company completed a $3.0 million registered direct offering for the sale of 3,571,431 shares of the Company’s common stock at a purchase price of $0.84 per share.
Federal Grants – Funding under federal grants was $1.4 million for the fourth quarter of 2022 compared to $1.6 million in the comparable year ago quarter. For the full year 2022, funding from federal grants was $2.5 million compared to $3.5 million for full year 2021. The differences are primarily related to both pre-clinical and clinical activities for the MPARTM program.
Research & Development Expenses – R&D expenses were $6.4 million for the fourth quarter of 2022 compared to $2.2 million for the same period in 2021 and $19.8 million for the full year of 2022 compared to $4.7 million for the full year of 2021. The increases were primarily the result of increased external research and development costs related to the clinical programs for PF614 and PF614-MPAR.
General & Administrative Expenses – G&A expenses were $1.2 million for the fourth quarter of 2022 compared to $1.5 million for the same period of 2021 and $6.9 million for the full year of 2022 compared to $18.7 million for the full year of 2021. The decrease for the full year period was primarily driven by a one-time $11.6 million non-cash expense related to warrants issued under a share subscription facility.
Other Income (Expense) – Total other income (expense), net was income of $0.7 million for the fourth quarter of 2022 compared to expense of $8.0 million for the same period of 2021. For the full year periods, total other income (expense), net was income of $0.0 million in 2022 compared to expense of $9.3 million in 2021. The change in other expenses is primarily due to non-cash fair value adjustments for convertible notes and warrants.
Net Loss – Net loss for the fourth quarter of 2022 was $5.5 million compared to $10.0 million for the fourth quarter of 2021. For the full year of 2022, net loss was $24.2 million compared to $29.1 million for the full year of 2021. As a clinical stage biotech company, our continued research and development efforts toward regulatory approvals for our product candidates are expected to result in losses for the foreseeable future.
Corporate Update Conference Call

As previously announced, CEO, Dr. Lynn Kirkpatrick, CFO, Dave Humphrey, and CMO, Dr. William Schmidt, will host a conference call on Tuesday, April 11, 2023, at 11:00am ET to provide a corporate update and review the recently released results from the oral HAP study of PF614. The call will conclude with Q&A from participants. An accompanying presentation will be posted prior to the call to the Company’s investor relations website.

Date: Tuesday, April 11, 2023
Time: 11:00am ET
U.S. Dial-in: 1-877-407-0792
International Dial-in: 1-201-689-8263
Webcast: ENSC Corporate Update Call

Please dial in at least 10 minutes before the start of the call to ensure timely participation. A playback of the call will be available through Tuesday, May 9, 2023. To listen, call 1-844-512-2921 within the United States and Canada or 1-412-317-6671 when calling internationally. Please use the replay pin number 13737179.

Ensysce Biosciences, Inc.
Condensed Consolidated Statements of Operations

2021 2020 2021 2020
Three Months Ended December 31,
Year Ended
December 31,
2022 2021 2022 2021
Federal grants
$ 1,433,463 $ 1,635,292 $ 2,523,383 $ 3,531,199
Operating expenses:
Research and development
6,441,927 2,187,850 19,835,875 4,690,082
General and administrative
1,192,322 1,454,187 6,909,603 18,711,548
Total operating expenses
7,634,249 3,642,037 26,745,478 23,401,630
Loss from operations
(6,200,786 ) (2,006,745 ) (24,222,095 ) (19,870,431 )
Total other income (expense), net
722,710 (8,030,379 ) 14,410 (9,275,470 )
Net income (loss)
$ (5,478,076 ) $ (10,037,124 ) $ (24,207,685 ) $ (29,145,901 )
Adjustments to net income (loss)
(43,832 ) (802,926 ) (877,811 ) (740,950 )
Net income (loss) attributable to common stockholders
$ (5,521,908 ) $ (10,840,050 ) $ (25,085,496 ) $ (29,886,851 )
Net income (loss) per share attributable to common stockholders, basic and diluted
$ (1.52 ) $ (8.93 ) $ (11.62 ) $ (29.64 )
Ensysce Biosciences, Inc.
Condensed Consolidated Statements of Cash Flows

2021 2020
Year Ended December 31,
2022 2021
Net cash used in operating activities
$ (17,887,439 ) $ (8,242,177 )
Net cash provided by investing activities
4,500 -
Net cash provided by financing activities
8,765,905 20,312,699
Change in cash and cash equivalents
(9,117,034 ) 12,070,522
Cash and cash equivalents at beginning of period
12,264,736 194,214
Cash and cash equivalents at end of period
$ 3,147,702 $ 12,264,736
Ensysce Biosciences, Inc.
Condensed Consolidated Balance Sheets

December 31, December 31,
2022 2021
Assets
Current assets:
Cash and cash equivalents
$ 3,147,702 $ 12,264,736
Prepaid expenses and other current assets
2,151,467 3,397,857
Total current assets
5,299,169 15,662,593
Other assets
585,883 754,756
Total assets
$ 5,885,052 $ 16,417,349
Liabilities and stockholders’ deficit
Current liabilities:
Accounts payable
$ 2,943,791 $ 301,104
Accrued expenses and other liabilities
2,253,809 3,432,407
Notes payable and accrued interest
4,266,610 12,748,155
Total current liabilities
9,464,210 16,481,666
Long-term liabilities
450,494 8,093,741
Total liabilities
9,914,704 24,575,407
Stockholders’ deficit
(4,029,652 ) (8,158,058 )
Total liabilities and stockholders’ equity
$ 5,885,052 $ 16,417,349

On March 30, 2023 Cardinal Health (NYSE: CAH) reported that it has plans to release third-quarter financial results for its fiscal year 2023 on May 4, prior to the opening of trading on the New York Stock Exchange (Press release, Cardinal Health, MAR 30, 2023, View Source [SID1234629601]). The company will webcast a discussion of these results beginning at 8:30 a.m. Eastern.

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To access the webcast and corresponding slide presentation, visit Cardinal Health’s Investor Relations page. No access code is required. Presentation slides and a webcast replay will be available on the Investor Relations page for 12 months.

On March 30, 2023 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, reported its financial results for the fourth quarter and full year ended December 31, 2022 and provided an update on recent developments (Press release, IGM Biosciences, MAR 30, 2023, View Source [SID1234629589]).

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"During 2022 we continued to extend the application of our IgM antibody platform by preparing imvotamab for clinical trials in autoimmune diseases and signing an exclusive worldwide collaboration agreement with Sanofi to develop novel IgM agonist antibodies for oncology and autoimmune diseases," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "Also, and perhaps most significantly, the initial clinical results from IGM-8444, our anti-death receptor 5 IgM antibody, highlight the exciting potential of IgM antibodies as agonist antibody medicines. We are announcing today that we have dosed the first patient in our randomized clinical trial of IGM-8444 in combination with standard of care FOLFIRI chemotherapy and bevacizumab in second line metastatic colorectal cancer patients. We are also pleased with the expanded safety and efficacy data for imvotamab at 100 mg that we have developed through our non-Hodgkin’s lymphoma clinical trials, and we believe that imvotamab’s encouraging safety profile may be an important differentiating factor in the exciting new field of T cell engagers in autoimmune disease."

Mr. Schwarzer continued, "We expect that 2023 will also be an important year for the expansion and validation of IGM’s platform. Already this year, we have treated the first patients in our initial clinical study of IGM-7354, an IgM targeted immunostimulatory IL-15 cytokine, which could be used for the treatment of patients with solid and hematologic malignancies, potentially in combination with cellular therapies, such as CAR-T and CAR-NK cells. We are also initiating clinical studies of IGM-2644, our CD38 x CD3 T cell engaging IgM antibody, which we hope will prove to be a safe and more potent form of anti-CD38 therapy for multiple myeloma, including for patients who have previously been treated with daratumumab. We also plan to file Investigational New Drug applications and initiate clinical studies for imvotamab in multiple autoimmune diseases this year, beginning with systemic lupus erythematosus and rheumatoid arthritis."

Pipeline Updates

IGM-8444 (DR5)

First patient dosed in randomized colorectal cancer clinical trial. The Company announced today that it has treated the first patient in a randomized clinical trial of IGM-8444, an IgM agonist antibody targeting death receptor 5 (DR5), plus FOLFIRI and bevacizumab in second line metastatic colorectal cancer. The study is designed to assess the benefit of IGM-8444 when combined with the current standard of care regimen of FOLFIRI and bevacizumab. The Company will be assessing both the 3 mg/kg and 10 mg/kg dose levels of IGM-8444 with a primary endpoint of progression free survival and secondary endpoints of overall response rate and overall survival as compared to the current standard of care treatment arm.
Encouraging data in combination with FOLFIRI. As announced in January 2023, IGM-8444 showed an encouraging safety profile which was broadly comparable to that expected from chemotherapy alone in this setting. Specifically, no signs of drug related clinically significant hepatotoxicity were observed, as only Grade 1 and Grade 2 transient drug related liver enzyme elevations were seen. In patients with metastatic colorectal cancer, the combination of IGM-8444 and FOLFIRI showed promising activity at 3 mg/kg, with multiple confirmed responses observed, including some in patients who had previously progressed on FOLFIRI.
Clinical biomarker data supports activity and dose response across multiple dose levels. Clinical biomarker data from 64 patients treated in monotherapy and combination dose cohorts across multiple dose levels of IGM-8444 in the Company’s ongoing Phase 1 clinical trial showed that virtually all of these patients (60 of 64) showed an increase in levels of the cell death biomarker caspase-3 following treatment with IGM-8444. This increase began to be seen after the initial dose of IGM-8444 and showed a trend towards a dose dependent increase between the two highest dose levels tested of 3 mg/kg and 10 mg/kg.
First patient dosed in venetoclax combination. The Company also announced today that it has dosed the first patient in its IGM-8444 plus venetoclax and azacytidine Phase 1 combination cohort in subjects with acute myeloid leukemia.
Dosing ongoing in the fifth birinapant dose cohort. The Company further announced today that it is currently treating patients in its fifth birinapant Phase 1 combination dose escalation cohort. To date, there have not been any observed dose limiting toxicities in combination with birinapant.
Imvotamab (CD20 x CD3)

Advancing into multiple autoimmune clinical trials. The Company announced today that it plans to file Investigational New Drug (IND) applications in the second quarter of 2023 this year to begin clinical testing of imvotamab in severe systemic lupus erythematosus and severe rheumatoid arthritis. The Company believes that the clinical safety and efficacy profile of imvotamab positions it very well for the exciting new area of treating autoimmune disease with T cell engagers.
Cytokine release incidence of less than 10% at 100 mg dose level. The Company announced today that as of its most recent data assessment the incidence of cytokine release syndrome was nine percent (9%) combined over all safety evaluable patients treated with the 100 mg titration weekly dosing regimen in its Phase 1 and Phase 2 non-Hodgkin’s lymphoma (NHL) studies.
DLBCL complete response rate greater than 30% at 100 mg dose level. The Company also announced today that, although the patient numbers are very small and additional patients currently on treatment may respond, as of its most recent data assessment it has achieved a complete response rate of greater than 30% combined over all efficacy evaluable diffuse large B cell lymphoma patients treated with the 100 mg titration weekly dosing regimen in its Phase 1 and Phase 2 NHL studies.
Redirecting clinical development efforts to autoimmune disease. In light of its plans for the extensive clinical development of imvotamab in autoimmune diseases and the limited commercial opportunities in monotherapy treatment of NHL, the Company announced today that it has decided to cease further monotherapy clinical development efforts for imvotamab in NHL. The Company continues to believe that the safety and efficacy profile of imvotamab positions it well as a combination partner for the treatment of NHL, and it plans to focus its future efforts in NHL on evaluating combination opportunities and partnerships for imvotamab.
IGM-7354 (IL-15 x PD-L1)

Phase 1 trial initiated. As previously announced, the Company has initiated a clinical trial exploring the safety, efficacy and biomarker activity of IGM-7354, an IgM targeted immunostimulatory IL-15 cytokine, in the treatment of patients with solid tumors.
First two patients dosed. The Company announced today that it has successfully dosed two patients in its clinical trial of IGM-7354 without any drug related safety issues to date.
Preclinical data presented. In November 2022, the Company presented preclinical results at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. The data was featured in a poster titled "IGM-7354, an anti-PD-L1/IL-15 IgM immunocytokine, activates and expands NK cells and effector memory CD8+ T cells in vivo".
IGM-2644 (CD38 x CD3)

IND clearance. The Company announced today that the U.S. Food and Drug Administration has cleared its IND application for a Phase 1 dose escalation trial of IGM-2644, a CD38 x CD3 IgM T cell engaging antibody, in patients with recurrent or refractory multiple myeloma. This study will investigate the initial safety and efficacy of IGM-2644 in patients who have progressed on previous therapies. The Company’s ultimate clinical development goal is to establish IGM-2644 as a safe and more potent anti-CD38 therapy, particularly for patients who have received prior daratumumab treatment.
Preclinical data. In December 2022, the Company presented preclinical data for IGM-2644 at the ASH (Free ASH Whitepaper) Annual Meeting and Exposition. The results were featured in a poster presentation titled "IGM-2644, a Novel CD38 x CD3 Bispecific IgM T Cell Engager Demonstrates Potent Efficacy on Myeloma Cells with an Improved Preclinical Safety Profile", which highlighted IGM-2644’s greater complement dependent cytotoxicity activity as compared to conventional IgG anti-CD38 antibodies. Additionally, IGM-2644 achieved potent T cell dependent cellular cytotoxicity (TDCC) killing of daratumumab-resistant cell lines with minimal cytokine release and potent TDCC killing of myeloma patient samples.
Fourth Quarter and Full Year 2022 Financial Results

Cash and Investments: Cash and investments as of December 31, 2022 were $427.2 million, compared to $229.5 million as of December 31, 2021.
Collaboration Revenue: For the fourth quarter and year ended 2022, collaboration revenues were $0.4 million and $1.1 million, respectively, compared to no revenue for the same period in 2021.
Research and Development (R&D) Expenses: For the fourth quarter and year ended 2022, R&D expenses were $45.0 million and $179.3 million, respectively, compared to $39.2 million and $127.0 million for the fourth quarter and year ended 2021, respectively.
General and Administrative (G&A) Expenses: For the fourth quarter and year ended 2022, G&A expenses were $11.6 million and $49.7 million, respectively, compared to $11.5 million and $38.3 million for the fourth quarter and year ended 2021, respectively.
Net Loss: For the fourth quarter of 2022, net loss was $52.6 million, or a loss of $1.19 per share, compared to a net loss of $50.6 million, or a loss of $1.50 per share, for the fourth quarter of 2021. For the year ended 2022, net loss was $221.1 million, or a loss of $5.32 per share, compared to a net loss of $165.2 million, or a loss of $4.93 per share, for the year ended 2021.
2023 Financial Guidance
The Company expects full year 2023 GAAP operating expenses of $290 million to $300 million, including estimated non-cash stock-based compensation expense of approximately $50 million, and full year collaboration revenue of approximately $3 million related to the Sanofi agreement. The Company expects to end 2023 with a balance of approximately $200 million in cash and investments, and for the balance to enable it to fund its operating expenses and capital expenditure requirements into the second half of 2024.

Conference Call and Webcast
IGM will host a live conference call and webcast at 4:30 p.m. EDT today, March 30, 2023, to discuss the Company’s financial results and provide a corporate update. The webcast can be accessed by clicking the link: View Source and will also be available on the "Events and Presentations" page in the "Investors" section of the Company’s website.