On March 30, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next generation therapeutics for cancer patients, reported that John Celebi, president and chief executive officer, will participate in a panel titled ‘Novel Approaches in Immunotherapy’ at Cantor Fitzgerald’s Future of Oncology Virtual Symposium on Monday, April 3rd at 10:00 a.m. ET (Press release, Sensei Biotherapeutics, MAR 30, 2023, View Source [SID1234629671]).

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On March 30, 2023 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies ("ETBs"), to create novel therapies with potent differentiated mechanisms of action for cancer, reported financial results for the fourth quarter and full year ended December 31, 2022 (Press release, Molecular Templates, MAR 30, 2023, View Source [SID1234629667]). MTEM also announced a strategic reprioritization and corresponding reduction in workforce, in order to focus on its core clinical development programs and extend its financial runway.

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Strategic Reprioritization and Cost-Saving Measures

On March 29, 2023, the Board of Directors of MTEM approved a strategic reprioritization and corresponding reduction in workforce, designed to focus on the clinical development programs for MT-6402 (PD-L1), MT-8421 (CTLA-4), and MT-0169 (CD38), and preclinical activities related to MTEM’s collaboration with Bristol Myers Squibb. This restructuring will reduce MTEM’s workforce by approximately 50%, result in the cessation of the MT-5111 (HER2) clinical development program, and focus the majority of MTEM’s preclinical efforts around activities related to the Bristol Myers Squibb collaboration.

Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated: "These cost-savings measures are a difficult, but necessary, step for MTEM to take in order to continue pursuing the development of these promising programs. We thank all our employees who have worked so hard to bring these programs this far, and we will continue this important work with our refocused strategy and available resources." Dr. Poma added, "We have now seen evidence of monotherapy clinical activity with MT-6402 through two separate mechanisms of action unique to immuno-oncology: the alteration of tumor immunophenotype and the dismantling of the tumor microenvironment (‘TME’). We recently announced the FDA’s acceptance of our Investigational New Drug Application (‘IND’) for MT-8421, a new approach to CTLA-4 that we believe can potently deplete Tregs in the TME without driving immune-related adverse events (‘irAEs’). We look forward to providing further updates on our MT-6402, MT-8421 and MT-0169 programs throughout 2023."

Company Highlights

MTEM expects to provide periodic updates on MT-6402, MT-8421, and MT-0169 throughout 2023.
Clinical data for each program has demonstrated novel mechanisms of action, unique pharmacodynamic ("PD") effects, and single agent activity in heavily relapsed / refractory patients across immuno-oncology, hematologic, and solid tumor indications.
Dose escalation continues for MT-6402. MTEM observed dose-dependent PD effects not seen with PD-(L)1 antibodies and consistent with T-cell activation and TME dismantling. Maximal MDSC depletion was observed at 63 mcg/kg, the highest dose cleared to date. PD effects were seen across patients, irrespective of HLA genotype or level of tumor or immune cell PD-L1 staining.
Seven patients were evaluable for radiographic assessment at the end of cycle 2 in the 63 mcg/kg cohort for MT-6402. One patient with nasopharynx squamous cell carcinoma in this cohort had a PR (RECIST) with a 63% reduction in the index lesion after cycle 2 which was maintained and confirmed at the end of cycle 4 (66% reduction). The patient remains on study.
One patient in cohort 1 (16 mcg/kg) for MT-6402 with non-small cell lung cancer ("NSCLC") demonstrated resolution of three osseous lesions and a reduction in uptake in the remaining lesion. This patient remained on treatment for approximately 8 months.
An IND for MT-8421 was accepted on March 8, 2023, with the first-in-human phase I study anticipated by mid-year 2023. MT-8421 targets CTLA-4-expressing Tregs in the TME for elimination without affecting Tregs in the periphery.
Dose escalation continues for MT-0169. MT-0169 completed the 5 mcg/kg dose escalation cohort (N=4) and the 10 mcg/kg dose escalation cohort (N=3) without any cardiac AEs or dose-limiting toxicities ("DLTs") and is enrolling at 15 mcg/kg. A Very Good Partial Response ("VGPR") was seen in a patient with extramedullary IgA myeloma treated at 5 mcg/kg which improved to a stringent Complete Response at cycle 8. The patient remains on study.
Of the over 100 patients treated across MTEM’s three clinical programs utilizing our de-immunized scaffold to date, there have been no instances of capillary leak syndrome or other manifestations of innate immunity observed.
Nearly all toxicities seen to date appear to be target-mediated with no non-specific scaffold effects noted, apart from occasional episodes of an infusion related reaction. No instances of off-target hematologic toxicity, interstitial lung disease, hepatic toxicity, or ocular toxicity common with antibody-drug conjugates have been observed.
The ETB platform continues to demonstrate clinical validation in terms of both safety and efficacy.
MT-6402 (PD-L1-targeting ETB with Antigen Seeding Technology)

MT-6402 was designed to activate T-cells through direct cell-kill of immunosuppressive PD-L1+ immune cells.
In addition, MT-6402 can deliver and induce the presentation of an MHC class I CMV antigen on tumor cells (antigen seeding mechanism of action) for pre-existing CD8 T-cell recognition and destruction in HLA-A*02/CMV+ patients with high PD-L1 expression on their tumors.
MT-6402 continues to demonstrate PD effects and monotherapy activity in heavily pre-treated checkpoint therapy experienced patients.
Dose escalation continues in the MT-6402 phase I study in relapsed/refractory solid tumor patients with PD-L1-expressing tumors and/or PD-L1 expressing immune cells in the TME.

Highlights from the on-going Phase I study include:

MTEM continues to observe PD effects not seen with PD-(L)1 antibodies and consistent with T-cell activation and TME dismantling. Maximal MDSC depletion was observed at 63 mcg/kg, the highest dose cleared to date. PD effects were seen across patients, irrespective of HLA genotype or level of tumor or immune cell PD-L1 staining.
Seven patients were evaluable for radiographic assessment at the end of cycle 2 in the 63 mcg/kg cohort. One patient in this cohort had a PR (RECIST) with a 63% reduction in the index lesion after cycle 2 which was maintained and confirmed at the end of cycle 4. This is a patient with metastatic squamous cell nasopharynx carcinoma ("NPC") with disease progression after radiation therapy, chemotherapy, and pembrolizumab who had 2% PD-L1 expression and is not HLA-A*02, suggesting that the response is due to T-cell activation through the clearance of PD-L1+ immune cells, a novel mechanism in immuno-oncology. The patient showed a >250% increase in their CD8/CD4 T-cell ratio. The patient remains on study in the fifth month of therapy.
One patient in cohort 1 (16 mcg/kg) with NSCLC demonstrated resolution of three osseous lesions and a reduction in uptake in the remaining lesion. This patient also experienced grade 2 cytokine release syndrome consistent with T-cell activation and was dose reduced to 8 mcg/kg. This patient is the only patient treated thus far with high tumor PD-L1 expression who is also HLA-A*02/ CMV+ and hence appropriate for the antigen seeding mechanism of action. Antigen seeding and the alteration of tumor immunophenotype is a novel mechanism in immuno-oncology unique to the ETB scaffold.
Treatment-related AEs including immune-related AEs have been largely restricted to grade 1-2. The 63 mcg/kg dose was well-tolerated and dose escalation continues at 83 mcg/kg.
Two Phase I dose expansion cohorts are planned for 2023 including for patients with high PD-L1 tumor expression and for patients with low PD-L1 tumor expression.
MT-8421 (CTLA-4 ETB)

MT-8421 was designed to target CTLA-4 in a wholly distinct manner from the current monoclonal antibody approaches. MT-8421 was designed to eliminate CTLA-4-expressing Tregs in the TME through a direct cell-kill mechanism independent of the effector cell presence that antibodies rely upon.
MT-8421 was also designed to avoid CTLA-4 blockade in the periphery, the major mechanism of antibody-mediated autoimmune toxicity.
MTEM has received clearance by the United States Food and Drug Administration ("FDA") following review of its IND to proceed for clinical testing of its novel MT-8421 ETB program targeting CTLA-4 in patients with relapsed/refractory solid tumors previously exposed to checkpoint inhibitors.
MTEM expects to initiate a first-in-human Phase I study with MT-8421 by mid-year 2023.
MT-0169 (CD38 ETB)

MT-0169 was designed to destroy CD38+ tumor cells through internalization of CD38 and cell destruction via a novel mechanism of action (enzymatic ribosomal destruction and immunogenic cell death). Highlights from the on-going Phase I include:
The 5 mcg/kg cohort completed recruitment (N=4) and analysis with no related AEs higher than grade 1 and no cardiac AEs.
A VGPR was seen in a patient with extramedullary IgA myeloma treated at 5 mcg/kg. The patient had a marked reduction in IgA serum protein, conversion from immunofixation positive to negative, and significant improvement of hemoglobin to normal values without transfusion. The patient’s disease was quad-agent refractory including CD38-targeting, proteosome inhibitor, IMiD, and a BCMA bispecific antibody. The patient’s response improved to a stringent Complete Response and they remain on study.
Dose escalation completed with three patients enrolled at 10 mcg/kg and no related AE’s higher than grade 2.
Dose escalation is now proceeding at 15 mcg/kg.
Key Milestones for 2023

Accelerating enrollment across all clinical programs with advancement into later stage trials expected in 2023
Initiation of first-in-human Phase I study for MT-8421
Advancement of Bristol Myers Squibb research collaboration across multiple targets
Conferences

MTEM participated in the Breast and Lung Cancer Panel at TD Cowen 43rd Annual Health Care Conference, which took place in Boston, Tuesday, March 7, 2023, 10:30am – 11:30am ET. The webcast can be accessed here and in the "News and Media" section of the corporate website.
MTEM presented a fireside chat at the virtual Oppenheimer 33rd Annual Healthcare Conference, which took place Wednesday, March 15, 2023, 12:40am ET. The webcast can be accessed here and in the "News and Media" section of the corporate website.
MTEM will present an abstract, "Engineered Toxin Bodies (ETBs): Clinical stage immunotoxins with a safer and differentiated profile", Monday, April 17, 2023, 1:30pm – 5pm ET (Section 13, Poster Board No 29, No. 2661), at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting taking place at the Orange County Convention Center in Orlando, FL from April 14 – 19, 2023.
Financial Results

The net loss attributable to common shareholders for the fourth quarter of 2022 was $22.0 million, or $0.39 per basic and diluted share. This compares with a net loss attributable to common shareholders of $10.2 million, or $0.18 per basic and diluted share, for the same period in 2021.

Revenues for the fourth quarter of 2022 were $2.6 million, compared to $18.0 million for the same period in 2021. Revenues for the fourth quarter of 2022 were comprised of revenues from collaborative research and development agreements with Bristol Myers Squibb.

Total research and development expenses for the fourth quarter of 2022 were $17.6 million, compared with $19.3 million for the same period in 2021. Total general and administrative expenses for the fourth quarter of 2022 were $6.1 million, compared with $7.9 million for the same period in 2021.

As of December 31, 2022, MTEM’s cash and investments totaled $61.0 million, including borrowings of $35.0 million under its K2 Loan and Security Agreement whose scheduled maturity date for repayment is June 1, 2024, subject to continued compliance with the financial covenant and solvency requirements therein. MTEM is currently in compliance with such covenant and requirements, and expects to continue to be in compliance into the fourth quarter of 2023. Any default of the financial covenant or solvency requirements would potentially trigger accelerated repayment. Subject to MTEM’s continued compliance with the K2 Loan and Security Agreement, MTEM anticipates a cash runway into the second quarter of 2024.

On March 30, 2023 Galapagos NV (Euronext & NASDAQ: GLPG) and NovAliX reported a strategic collaboration in which Galapagos’ research and discovery capabilities and exclusively related employees based in Romainville, France, will be transferred to NovAliX, a drug discovery-focused Contract Research Organization (Press release, Galapagos, MAR 30, 2023, View Source [SID1234629655]). The agreement follows Galapagos’ renewed focus on its key therapeutic areas of oncology and immunology, and the strategic reorientation of the company into a fit-for-purpose research and development (R&D) organization which aims to accelerate innovation, reduce risks and shorten drug development timelines.

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Under the terms of the agreement, NovAliX will acquire Galapagos’ drug discovery and research activities conducted in Romainville, France. As a result of the acquisition Galapagos’ employees in Romainville who are exclusively dedicated to the operation of these activities will be transferred to NovAliX who is dedicated to assuming all ongoing research and discovery activities in Romainville. In return, Galapagos is committed to utilizing the research capabilities and expertise of NovAliX through a five year-collaboration and within the context of the company’s R&D portfolio. The financial impact is included in Galapagos’ previously announced 2023 cash burn guidance in the range of €380-420 million. The transaction is subject to customary closing conditions and is anticipated to close in July 2023.

"Last year, we announced our Forward, Faster strategy, and the strategic reorientation of our company into a fit-for-purpose R&D organization. In light of our renewed focus and our goal to safeguard the continued employment of our colleagues at our research site in Romainville, we are extremely pleased that we have come to an agreement with NovAliX," commented Paul Stoffels1, CEO and Chairman of Galapagos. "I would like to thank our teams and NovAliX for their trust and commitment throughout the past several months to make this happen. I am confident that our transferred colleagues together with the teams at NovAliX will thrive and that they will continue to contribute to the future success of Galapagos as part of this long-term collaboration."

"We are extremely pleased to enter into an integrated drug discovery collaboration with Galapagos. The acquisition of Galapagos’ drug discovery and research activities in Romainville, including its highly skilled team, is the perfect fit for NovAliX in order to complement our DNA-Encoded-Libraries database2 and cryo-EM3 driven discovery engine. It positions us as a key player in the field, offering the full scope of drug discovery capabilities and innovative technologies in kidney diseases, fibrosis and immunology, complementing our existing expertise in oncology and infectious diseases," said Stephan Jenn, President of NovAliX. "This further demonstrates that we are executing on our growth strategy and our ambition to expand our service offering beyond early research. It highlights the evolution that is taking place in our sector, with the emergence of new partnership models between CROs and the biopharmaceutical industry to accelerate therapeutic innovation. We look forward to our long-term collaboration and to welcoming the Galapagos’ teams.

On March 30, 2023 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported financial results for the full-year ended December 31, 2022, and recent corporate highlights (Press release, Checkpoint Therapeutics, MAR 30, 2023, View Source [SID1234629653]).

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James F. Oliviero, President and Chief Executive Officer of Checkpoint, said, "The past year was a momentous one for Checkpoint, and we began 2023 with the submission of our Biologics License Application ("BLA") to the U.S. Food and Drug Administration ("FDA") seeking approval of cosibelimab, our 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. Our BLA submission was subsequently accepted for filing and is under active review with a Prescription Drug User Fee Act ("PDUFA") goal date of January 3, 2024."

"This initial indication for cosibelimab represents a potential $1.6 billion U.S. market opportunity," continued Oliviero. "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 who are currently underserved by available therapies."

2022 and Recent Corporate Highlights:

Checkpoint submitted a BLA to the FDA seeking approval of cosibelimab in January 2023. In March 2023, the FDA accepted for filing the BLA for cosibelimab and set a 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.
In January 2022, Checkpoint announced positive top-line results from its registration-enabling clinical trial evaluating the safety and efficacy of 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 May 2022, Checkpoint announced that it received Pediatric Investigation Plan product-specific waivers from the European Medicines Agency and the U.K. Medicines & Healthcare products Regulatory Agency for cosibelimab in cSCC. The waivers remove the requirement to conduct pediatric clinical studies to support cosibelimab marketing authorization applications in Europe.

In June 2022, Checkpoint announced that the top-line results of its 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 presented included confirmed ORR by independent central review in the modified intent-to-treat 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, Checkpoint announced positive interim results from its 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 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. Checkpoint also reached agreement with the FDA on all key aspects discussed regarding the content of the BLA submission.
In December 2022, Checkpoint completed a registered direct offering priced At-the-Market under Nasdaq rules, for total gross proceeds of approximately $7.5 million.
In February 2023, Checkpoint completed another registered direct offering priced At-the-Market under Nasdaq rules and a concurrent private placement of two series of warrants to purchase Checkpoint common stock, for total gross proceeds of approximately $7.5 million.
Financial Results:

Cash Position: As of December 31, 2022, Checkpoint’s cash and cash equivalents totaled $12.1 million, compared to $54.7 million at December 31, 2021, a decrease of $42.6 million. This cash position is not reflective of the registered direct offering closed in February 2023 for total gross proceeds of approximately $7.5 million.
R&D Expenses: Research and development expenses for the year ended December 31, 2022, were $49.8 million, compared to $48.5 million for the year ended December 31, 2021, an increase of $1.3 million. Research and development expenses for the year ended December 31, 2022 included $2.8 million of non-cash stock expenses, compared to $7.3 million in non-cash stock expenses for the year ended December 31, 2021.
G&A Expenses: General and administrative expenses for the year ended December 31, 2022, were $8.7 million, compared to $8.5 million for the year ended December 31, 2021, an increase of $0.2 million. General and administrative expenses for the year ended December 31, 2022 included $2.5 million of non-cash stock expenses, compared to $3.5 million in non-cash stock expenses for the year ended December 31, 2021.
Net Loss: Net loss attributable to common stockholders for the year ended December 31, 2022 was $62.6 million, or $7.09 per share, compared to a net loss of $56.7 million, or $7.45 per share, for the year ended December 31, 2021.

On March 30, 2023 Lisata Therapeutics, Inc. (Nasdaq: LSTA) ("Lisata" or the "Company"), a clinical-stage pharmaceutical company developing innovative therapies for the treatment of advanced solid tumors and other serious diseases, provided a business update and reports financial results for the three and twelve months ended December 31, 2022 (Press release, Caladrius Biosciences, MAR 30, 2023, View Source [SID1234629652]).

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"Last year (2022) was a year of major transformation, excitement and renewed energy for Lisata, allowing us to enter 2023 with growing momentum as we continue to build an enduring pharmaceutical company," stated David J. Mazzo, Ph.D., Chief Executive Officer of Lisata. "We believe in the potential of our new development pipeline and take pride in the advancement of our clinical studies in oncology and other serious diseases. LSTA1, our lead investigational product candidate from the CendR Platform, is the subject of multiple planned and ongoing clinical trials being conducted globally in a variety of solid tumor types and in combination with several anti-cancer agents. Based on substantial preclinical and, importantly, early human clinical data, we believe that LSTA1 has the potential to become an integral part of a revised standard-of-care therapy for many difficult to treat cancers.
Dr. Mazzo continued, "We are dedicated to continued efficient execution of our studies and, eventually, to producing definitive data hopefully confirming the promise of our clinical development pipeline. We anticipate that such execution and those data will result in increased shareholder value while prompting additional attractive partnering opportunities. I look forward to providing further updates on our progress in the coming weeks and months."
Development Portfolio Update

LSTA1 (formerly CEND-1) as a treatment for solid tumor cancers in combination with other anti-cancer agents

LSTA1 is an investigational drug designed to activate a novel uptake pathway that allows co-administered or tethered anti-cancer drugs to penetrate solid tumors more effectively. LSTA1 actuates this active transport system in a tumor-specific manner, resulting in systemically co-administered anti-cancer drugs more efficiently penetrating and accumulating in the tumor, while normal tissues are not affected. LSTA1 also has the potential to modify the tumor microenvironment, with the objective of making tumors more susceptible to immunotherapies. We and our collaborators have amassed significant non-clinical data demonstrating enhanced delivery of a range of emerging anti-cancer therapies, including immunotherapies and RNA-based therapeutics. To date, LSTA1 has also demonstrated favorable safety, tolerability and activity in completed and ongoing clinical trials designed to test its ability to enhance delivery of standard-of-care chemotherapy for pancreatic cancer. Currently, LSTA1 is the subject of Phase 1b/2a and 2b clinical studies being conducted globally in various solid tumors, including metastatic pancreatic ductal adenocarcinoma, in combination with a variety of anti-cancer regimens. The combination of LSTA1 with corresponding standards-of-care in other solid tumor indications is planned for clinical study in the first half of 2023.

HONEDRA (LSTA12, formerly CLBS12) for the treatment of critical limb ischemia ("CLI")

HONEDRA is the Company’s SAKIGAKE-designated product candidate for the treatment of CLI and Buerger’s disease in Japan, which is now in the pre-consultation phase of the registration process with the Pharmaceuticals and Medical Devices Agency ("PMDA") in Japan. Data from the follow-up of all patients completed in the registration-eligible clinical trial in Japan have been compiled and are being reviewed by the PMDA, after which the PMDA is expected to provide important perspective to be considered in preparation for the formal consultation meetings which precede the Japanese new drug application. If successful in the pre-consultation process, Lisata expects formal clinical consultation to occur during 2023. Concomitantly, the Company has reinforced its efforts to secure a Japanese partner to complete the remaining steps of registration as well as eventual commercialization in Japan.

XOWNA (LSTA16, formerly CLBS16) for the treatment of coronary microvascular dysfunction ("CMD")

XOWNA is an experimental regenerative therapy for the treatment of CMD. It was the subject of a positive Phase 2a study (the "ESCaPE-CMD trial") reported in 2020 as well as the FREEDOM Trial, a Phase 2b study conducted in the U.S. The FREEDOM Trial was originally designed as a 105-patient double-blind, randomized, placebo-controlled trial to further evaluate the efficacy and safety of intracoronary delivery of autologous CD34+ cells (XOWNA) in subjects with CMD and without obstructive coronary artery disease and was expected to complete enrollment in approximately 12 months. As previously disclosed, enrollment in the FREEDOM Trial initially proceeded as planned with the first patient treated in January 2021; however, the impact of the COVID-19 pandemic in the U.S., coupled with supply chain issues associated with the catheters used for diagnosis of CMD and/or administration of XOWNA, as well as with a contrast agent typically used in many catheter laboratories, have made and continue to make enrollment much slower than originally predicted and challenging to accelerate. As a result, the Company announced that enrollment in the FREEDOM Trial had been suspended and that it intended to conduct an interim analysis of the data from not less than the first 20 patients enrolled using the 6-month follow-up data to evaluate the efficacy and safety of XOWNA in subjects with CMD. Based on that and the input of Key Opinion Leaders, the Company determined that execution of a redesigned FREEDOM-like trial would be the appropriate next step, but the cost of such a trial would be prohibitively expensive to undergo alone. Accordingly, the Company’s board of directors concluded that XOWNA development will only be continued if a strategic partner that can contribute the necessary capital for a redesigned trial is identified and secured.

LSTA201 (formerly CLBS201) for the treatment of diabetic kidney disease ("DKD")

Progressive kidney failure is associated with attrition of the microcirculation of the kidney. Preclinical studies in kidney disease and injury models have demonstrated that protection or replenishment of the microcirculation results in improved kidney function. Based on these observations, the Company initiated a Phase 1b, open-label, proof-of-concept trial evaluating LSTA201, a CD34+ regenerative cell therapy investigational product for intra-renal artery administration in patients with DKD. Patients selected for the study were in the pre-dialysis stage of kidney disease and exhibited rapidly progressing stage 3b disease. The protocol provided for a cohort of six patients overseen by an independent Data Safety Monitoring Board with the objective of determining the tolerance of intra-renal cell therapy injection in DKD patients as well as the ability of LSTA201 to regenerate kidney function. The principal read-out of data was based on the 6-month follow-up visit for all patients. A key criterion for continued development of LSTA201 was determined, a priori, to be the ability of LSTA201 to demonstrate a therapeutic effect that will make it competitive in the field of DKD treatment, i.e., kidney function regeneration, as indicated by increased Glomerular Filtration Rate ("GFR"). The Company treated the first patient in the LSTA201 proof-of-concept study in April 2022 and completed treatment for all six subjects during the third quarter of 2022. Top line results, which were reported on February 6, 2023, showed that LSTA201 was safe and well-tolerated by patients with no serious adverse events related to the therapy. However, the study did not demonstrate a consistent improvement in kidney function among patients. Nevertheless, the Company, based on the encouragement of the study’s principal investigator/key opinion leader, believes there may still be potential for use of CD34+ cell therapy for the treatment of DKD. However, it is expected that further development of LSTA201 would require significantly larger studies and capital investment. Thus, LSTA201 development will only be continued if a strategic partner that can contribute the necessary capital for future development is identified.

Fourth Quarter and Full Year 2022 Financial Highlights

Research and development expenses for the fourth quarter of 2022 were $3.2 million, a 22% decrease compared with $4.1 million for the fourth quarter of 2021, and $13.1 million for the year ended December 31, 2022 compared to $17.6 million for the year ended December 31, 2021, representing a decrease of approximately 26%. This was primarily due to a decrease in expenses associated with our XOWNA Phase 2b study (the FREEDOM Trial) as a result of the suspension in enrollment which commenced in the second quarter of 2022 and study close out activities in the third quarter of 2022, a decrease in expenses associated with HONEDRA in Japan related to study close out costs and one off recruiting expenses and interim chief medical officer consulting expenses in the prior year partially offset by the addition of manufacturing activities for LSTA1 and enrollment activities for the AGITG ASCEND study.

Research and development in both periods related to:

•Expenses associated with our XOWNA Phase 2b study (the FREEDOM Trial);
•Expenses associated with our registration-eligible study for HONEDRA in critical limb ischemia in Japan as well as corresponding regulatory discussions support expenses;
•Expenses associated with the preparation of our filing of an Investigational New Drug Application, as well as study execution expenses for the clinical study of LSTA201 for treatment of DKD; and
•Expenses associated with the addition of manufacturing activities for LSTA1, enrollment activities for the LSTA1 Phase 2b ASCEND study and preparatory activities associated with the design of a planned LSTA1 proof-of-concept basket trial in various solid tumors and in combination with the corresponding standards of care.
General and administrative expenses, which focus on general corporate related activities, were $3.3 million for the three months ended December 31, 2022, representing an increase of 22% compared to $2.7 million for the three months ended December 31, 2021, and $14.1 million for the year ended December 31, 2022, representing an increase of 23% compared to $11.5 million for the year ended December 31, 2021. This was primarily due to a one-time increase in fees associated with the review of potential strategic transactions and merger related costs, an increase in equity expense as a result of performance stock unit vesting, merger option assumption expense and departing board member restricted stock unit vesting in addition to an increase in expenses associated with our annual stockholder meeting. Our general and administrative expenses are comprised of general corporate-related activities.

Overall, net losses were $54.2 million (includes non-routine merger related in-process research and development expense of $30.4 million) and $27.5 million for the years ended December 31, 2022 and 2021, respectively.

Balance Sheet Highlights

As of December 31, 2022, the Company had cash, cash equivalents and marketable securities of approximately $69.2 million. Current projections predict operating cash through the first half of 2025, encompassing anticipated data milestones from several ongoing and/or planned clinical studies.

Conference Call Information

Lisata will hold a live conference call today, March 30, 2023, at 4:30 p.m. Eastern time to discuss financial results, provide a business update and answer questions.

The Company is utilizing a new conference call service. Those wishing to participate must register for the conference call by way of the following link: CLICK HERE TO REGISTER. Registered participants will receive an email containing conference call details for dial-in options. To avoid delays, we encourage participants to dial into the conference call fifteen minutes ahead of the scheduled start time.
A live webcast of the call will also be accessible under the Investors & News section of Lisata’s website and will be available for replay beginning two hours after the conclusion of the call for 12 months.