On March 29, 2024 Alphamab Oncology reported financial results for the full year ended December 31, 2023 and highlighted recent progress and upcoming milestones (Press release, Alphamab, MAR 29, 2024, View Source [SID1234644738]).

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Dr. Ting Xu, Chairman and CEO of Alphamab Oncology, commented, "In 2023, Alphamab Oncology continued to focus on addressing clinical needs and adhere to differentiated innovation. With one product already in the market and three in pivotal clinical trials, we will continue to refine our antibody engineering platform to develop safe, effective innovative anti-tumor drugs, while accelerating clinical development, product commercialization, and international collaboration."

Financial Summary

● For the year ended December 31, 2023, we recorded total revenue of RMB 218.77 million, a 31.12% year-on-year increase. Meanwhile, product revenue reached RMB 195.55 million, a 32.54% year-on-year increase.

● For the year ended December 31, 2023, our R&D expenditure amounted to RMB 407.52 million, decreased by 12.97% as compared with year 2022.

● For the year ended December 31, 2023, we recorded total loss of RMB 210.59 million, a 35.35% year-on-year decrease.

● The Company completed a placement with total net proceeds of approximately HK $376.2 million (equivalent to RMB 329.21 million) from the subscription. We have a healthy financial position, with cash reserves of RMB 1407.24 million as of December 31, 2023.

Business Highlights

Product Pipeline

Distinguished by a globally competitive pipeline, the Company specializes in antibody-drug conjugation, single domain antibody/monoclonal antibodies, and multi-functional antibodies. Notably, Envafolimab, the world’s first subcutaneously injectable PD-L1 inhibitor, received approval from Chinese authorities in 2021, offering widespread accessibility to cancer patients. Three additional products are currently in the advanced stages of clinical development. Furthermore, we have cultivated a series of early-stage assets, including two in phase I development.

KN046

KN046, a BsAb immune checkpoint inhibitor simultaneously targeting two clinically-validated immune checkpoints, PD-L1 and CTLA-4, representing a potential breakthrough, next-generation immuno-oncology blockbuster drug. Approximately 20 clinical trials of KN046 at different stages covering more than 10 types of tumors including NSCLC, TNBC, ESCC, HCC, PDAC and thymic carcinoma have been conducted in China, the United States and Australia. The results of these clinical trials have shown an advantage in survival for patients. Several registrational clinical trials of KN046 are currently being conducted.

Events during the Reporting Period

● In May 2023, the phase III clinical trial of KN046 in combination with the platinum-based chemotherapy in patients with advanced unresectable or metastatic squamous non-small cell lung cancer ("sq NSCLC") was recommended by the independent data monitoring committee to continue the study and collect further follow-up overall survival ("OS") data till final OS analysis.

● We achieved good tolerance and promising anti-tumor efficacy results in a phase I clinical trial of KN046 in the treatment of patients with advanced solid tumors (especially in nasopharyngeal carcinoma patients). Such results were published online in Journal for ImmunoTherapy of Cancer ("JITC"), the official journal of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) ("SITC"), in June 2023.

● In July 2023, the phase II clinical research results of KN046 monotherapy in the treatment of advanced NSCLC were published online in the European Journal of Cancer. Both 3mg/kg and 5mg/kg KN046 showed promising efficacy and favorable safety profile in advanced squamous and non-squamous NSCLC patients after failure of or intolerance to previous platinum-based chemotherapy.

● We achieved good tolerance and promising efficacy and safety signal in a phase II clinical trial of KN046 combined with axitinib in the first-line treatment for advanced NSCLC. Such results were presented at the 2023 European Society for Medical Oncology Congress (the "ESMO Congress") in October 2023.

● We achieved good tolerance and encouraging results, especially in OS benefit, in NSCLC patients who had failed prior immune checkpoint inhibitor(s) therapy in a phase I and a phase II clinical trials of KN046 in treatment of NSCLC. Such results were presented at the ESMO (Free ESMO Whitepaper) Congress in October 2023.

● We obtained encouraging efficacy results, especially in OS benefit, and a favorable safety profile in advanced NSCLC patients received epidermal growth factor receptor ("EGFR") sensitivity mutation who failed EGFR tyrosine kinase inhibitor(s) (EGFR TKI(s)) in a clinical trial of KN046 combined with chemotherapy for the treatment of NSCLC. Such results were presented at the ESMO (Free ESMO Whitepaper) Congress in October 2023.

● We achieved promising anti-tumor activity and tolerability in patients with refractory or metastatic thymic carcinoma who had at least received first-line chemotherapy in a phase II clinical trial of KN046. As of data cut-off date, August 30, 2023, the median OS was not mature, demonstrating an encouraging signal in survival benefit. Such results were presented at the ESMO (Free ESMO Whitepaper) Congress in October 2023.

● In November 2023, the interim analysis of phase III clinical trial of KN046 in combination with nab-paclitaxel/gemcitabine versus placebo in combination with nab-paclitaxel/gemcitabine, for the treatment of locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma without systemic treatment, was recommended by the independent data monitoring committee to continue the study and collect further follow-up OS data till final OS analysis.

Events after the Reporting Period

● We achieved encouraging PFS and OS benefit, good tolerance and manageable safety profile in a phase II clinical trial of KN046 in combination with nab-paclitaxel as the first-line treatment for advance triple-negative breast cancer. Such results were published in Nature Communications, in February 2024.

● We achieved considerable efficacy and good tolerance in a phase II clinical trial of KN046 in combination with chemotherapy as first-line treatment for metastatic NSCLC. Such results were published in Cell Reports Medicine, in March 2024.

Expected Milestones in 2024

● Perform final OS analysis of the phase III clinical trial of KN046 in combination with chemotherapy as the first-line treatment for sq NSCLC.

● Perform final OS analysis of the phase III clinical trial of KN046 in combination with chemotherapy as the first-line treatment for advanced pancreatic cancer.

● The relevant data from the phase II clinical trial of KN046 in combination with axitinib in the treatment for advanced NSCLC will be read out and expected to be presented at the ESMO (Free ESMO Whitepaper) Congress in October 2024.

KN026

KN026 is a next-generation anti-HER2 BsAb that can simultaneously bind two distinct clinically-validated epitopes of HER2, resulting in potentially superior efficacy. The phase I and phase II clinical trials of KN026 have shown promising early efficacy signals and favorable safety profile in the treatment of heavily pre-treated HER2 expressing cancers.

Events during the Reporting Period

● In May 2023, the investigational new drug ("IND") approval for a phase III clinical trial of KN026 in combination with docetaxel (albumin binding) in the first-line treatment for HER2-positive recurrent or metastatic breast cancer was granted by the NMPA.

● In June 2023，we achieved favorable efficacy and safety profile in a phase II clinical trial of KN026 in combination of KN046 in the treatment of locally advanced unresectable or metastatic HER2-positive solid tumors other than BC or GC/GEJ. Such results were presented at the 2023 ASCO (Free ASCO Whitepaper) annual meeting. For the enrolled 26 patients, the results showed promising clinical benefits as compared with existing therapies in terms of ORR, PFS, 12-month OS rate, and safety.

● In July 2023, the first patient was successfully dosed in a phase III clinical trial of KN026 in combination of HB1801, a kind of docetaxel for injection (albumin binding), as the first-line treatment for HER2-positive recurrent or metastatic breast cancer.

● KN026 in combination with docetaxel as first-line treatment for HER2-positive recurrent or metastatic breast cancer in a phase II clinical trial had shown a tolerated and promising clinical benefit. Such results were presented at the ESMO (Free ESMO Whitepaper) Congress 2023 in October 2023.

● We achieved promising clinical results for patients with HER2-positive early or locally advanced breast cancer with an acceptable and manageable safety profile in a phase II clinical trial of neoadjuvant treatment of KN026 in combination with docetaxel. Such results were presented at the ESMO (Free ESMO Whitepaper) Congress in October 2023.

● In November 2023, KN026 in combination with chemotherapy, has been granted breakthrough therapy designation for the treatment of patients with HER2-positive GC/GEJ who have failed first-line standard treatment (trastuzumab in combination with chemotherapy) by the Center for Drug Evaluation (the "CDE") of the NMPA.

● We achieved good tolerance and promising clinical benefit as the first-line treatment for HER2-positive recurrent or metastatic breast cancer in a clinical trial of KN026 in combination with docetaxel. Such results were presented at the 46th San Antonio Breast Cancer Symposium ("SABCS") in December 2023.

JSKN003

JSKN003, an anti-HER2 bispecific-antibody ADC based on KN026, is developed inhouse with proprietary Glycan-specific conjugation platform. Comparing its counterparts, JSKN003 demonstrated better serum stability, stronger bystander effect and comparable tumor killing activity, which effectively expands the therapeutic window.

Events during the Reporting Period

● In March 2023, the first patient was successfully dosed in a phase Ia/Ib clinical trial of JSKN003 conducted in China. This phase Ia/Ib clinical trial of JSKN003 was further approved by the ethical committee of its leading clinical site to be adjusted as a phase I/II clinical trial.

● As of October 26, 2023, JSKN003 has shown initial efficacy and has been well tolerated by the HER2-expressing solid tumors patients in the phase I clinical trial in Australia. The relevant clinical data were presented in the Company’s announcement on November 16, 2023.

● In December 2023, the first patient has been successfully dosed in the phase III clinical trial of JSKN003 for the treatment of advanced HER2-low expression breast cancer.

Expected Milestones in 2024

● Start two registrational clinical trials.

● Clinical data from the phase Ia (dose-escalation stage) of the clinical trial conducted in Australia of JSKN003 for the treatment of HER2-expressing advanced solid tumors will be presented at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in April 2024.

● Part of the data from the phase I clinical trial conducted in Australia and the phase I/II clinical trial conducted in China of JSKN003 are expected to be presented at the 2024 ASCO (Free ASCO Whitepaper) annual meeting in June 2024.

● Data of breast cancer patients from the phase I clinical trial conducted in Australia and the phase I/II clinical trial conducted in China of JSKN003 are expected to be presented at the SABCS in December 2024.

KN035 (Envafolimab)

KN035, an innovative anti-tumor immunotherapy drug, is the first subcutaneously injectable PD-L1 inhibitor worldwide, and the only immunotherapy drug aimed at cross-tumor indications and the first domestically produced PD-L1 drug, offering advantages in effectiveness, safety, convenience, compliance and lower medical cost. Envafolimab is currently being studied in multiple pivotal clinical trials in China and the United States.

Events during the Reporting Period

● In June 2023, the positive results of a six-month independent data monitoring committee review for the ongoing ENVASARC phase II pivotal clinical trial of KN035 were released by one of our collaboration partners, TRACON Pharmaceuticals, Inc.

● In August 2023, the IND approval for a phase III clinical trial of KN035 was granted by the NMPA for the neoadjuvant/adjuvant therapy in patients with resectable NSCLC, and the first patient was successfully dosed in December 2023.

● In October 2023, the IND approval for a phase III clinical trial of KN035 in combination with lenvatinib versus carboplatin-paclitaxel chemotherapy for the first-line treatment of patients with advanced or recurrent endometrial cancer with proficient mismatch repair (pMMR) was granted by the United States Food and Drug Administration (the "FDA").

● In November 2023, KN035 in combination with lenvatinib was granted breakthrough therapy designation for the treatment of non-metastatic advanced microsatellite instability-high (MSI-H)/non-mismatch-repair deficiency (dMMR) advanced endometrial cancer that has failed or intolerant of at least one prior line of platinum-based chemotherapy by the CDE of the NMPA.

Events after the Reporting Period

● In January 2024, Alphamab Oncology and 3D Medicines entered into a license agreement with Glenmark for the subcutaneous injection PD-L1 antibody drug KN035, pursuant to which, Glenmark was granted exclusive licensing interests in clinical development and commercialization of oncology indications of KN035 in India, Asia Pacific (except Singapore, Thailand, Malaysia), the Middle East and Africa, Russia, Commonwealth of Independent States and Latin America. Glenmark shall bear its own costs and expenses related to the development and commercialization of KN035 in the Field in the Territory. Jiangsu Alphamab retains the exclusive right to produce KN035 for any purpose either inside or outside the Territory.

JSKN033

JSKN033 is a subcutaneous injection compound consisting of JSKN003 and envafolimab.

● In December 2023, a phase I/II clinical trial of JSKN033 for the treatment of HER2- expressing advanced or metastatic solid tumors, has been approved by the Australian Bellberry Human Research Ethics Committee. And the first patient was successfully dosed in March 2024.

● The phase I dose escalation stage of the clinical trial of JSKN033 conducted in Australia is expected to be completed in 2024.

JSKN016

JSKN016, a bispecific antibody conjugated drug (ADC) simultaneously targeting HER3 (Human epidermal growth factor receptor 3) and TROP2 (Trophoblast cell surface antigen 2), which can induce apoptosis of TROP2 or HER3 positive tumor cells.

● In March 2024, the IND approval for a phase I clinical trial of JSKN016 in the treatment for advanced malignant solid tumors was granted by the CDE of the NMPA.

KN052

KN052, an innovative PD-L1/OX40 bispecific antibody, can simultaneously bind PD-L1 and OX40, effectively reversing tumor induced immune inhibition by blocking the PD-L1/PD-1 pathway and promoting the immune response by agonizing OX40.

● In February 2023, the Company entered into a strategic collaboration with Stemirna Therapeutics pursuant to which the Company will explore combination therapy of KN052 with personalized messenger ribonucleic acid ("mRNA") tumor vaccine SWP1001 in certain types of solid tumor.

● In March 2023, the pre-clinical research results of KN052 were accepted as Late-Breaking Research and were presented as poster at the 2023 AACR (Free AACR Whitepaper) annual meeting in April 2023. The pre-clinical data of KN052 demonstrated its acceptable pharmacokinetic and safety profile and that its anti-tumor activity is significantly stronger than that of the two single-target control antibodies used alone and in combination.

KN019

KN019, a CTLA-4-based immunosuppressant fusion protein, has potential broad applications in both autoimmune diseases and oncology treatment-induced immune disorders.

● In November 2023, the IND approval for the subcutaneous injection of KN019 was granted by the NMPA for clinical development.

Manufacturing Facilities

The Company’s R&D and industrialization base covers an area of 75 mu. The production line is equipped with world-class equipment that meets GMP regulations of NMPA, FDA, and EMA. We currently have a variety of engineered antibody drug production lines, including antibody drug substance workshops with a capacity of 12,000L, preparation workshops with capacity of more than 2.8 million vials per year and an ADC drug substance workshop. This facility can provide safe, effective, and cost controllable innovative drugs for cancer patients. We will promote the upgrade of ADC drug research and production processes in 2024.

On March 29, 2024 Biostar Pharma, Inc., the U.S. subsidiary of Beijing Biostar Pharmaceuticals Co., Ltd. which is a synthetic biology driven biopharma company focusing on the development and commercialization of innovative oncology drugs, reported that their core pipeline product utidelone injectable (UTD1) had been granted an Orphan Drug Designation (ODD) by the FDA for the treatment of breast cancer brain metastasis (BCBM) (Press release, Beijing Biostar Technologies, MAR 29, 2024, View Source [SID1234641631]).

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Up to 30% of metastatic breast cancer patients develop brain metastases (BM). Prognosis of patients with BM is poor and long-term survival is rare. Currently the survival duration of BCBM patients is very limited, with the median survival of only about 7.2 months, and even shorter for triple-negative breast cancer (TNBC) BM which is only 3.5 months. Macromolecular drugs usually cannot penetrate the blood-brain barrier (BBB), leading to low therapeutic efficacy. Therefore, local treatments including surgery and radiation therapy are currently considered the standard treatments for BCBM. As of now, there is only one drug approved for the treatment of BCBM globally, suggesting huge unmet medical needs [1].

Utidelone has the ability to cross BBB due to its unique physicochemical characteristic and insusceptibility to P-glycoprotein-mediated efflux. This ability has been well demonstrated by both preclinical and clinical studies. A phase II clinical trial of utidelone injectable in combination with etoposide and bevacizumab for HER2 negative BCBM patients (n=17) showed excellent central nervous system (CNS) overall response rate (ORR) and CNS clinical benefit rate (CBR) of 73% and 91%, respectively. Another phase II clinical trial of utidelone injectable in combination with bevacizumab for HER2 negative BCBM patients (n=46) demonstrated median PFS of 7.7 months and 12-month OS rate of 74.4%. The FDA granted ODD to utidelone injectable for the treatment of BCBM based on these promising data.

Considering utidelone’s excellent BBB-crossing capability and its therapeutic potential for brain tumors, Biostar Pharma also plans to advance the clinical studies of utidelone injectable for the treatments of other brain tumors such as lung cancer brain metastasis and glioma this year.

On March 29, 2024 IASO Bio, a biopharmaceutical company engaged in discovering, developing, manufacturing and marketing innovative cell therapies and antibody products, reported that China National Medical Products Administration (NMPA) has approved the Investigational New Drug (IND) application for Equecabtagene Autoleucel (IASO Bio R&D code: CT103A), a self-developed fully-human anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) autologous T-cell injection, for an expanded indication in treating relapsed and/or refractory multiple myeloma (R/RMM) patients who have undergone 1-2 lines of prior therapies and are refractory to lenalidomide (Press release, IASO Biotherapeutics, MAR 29, 2024, View Source;and-third-line-treatment-of-multiple-myeloma-302103455.html [SID1234641630]).

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The New Drug Application (NDA) for FUCASO (Equecabtagene Autoleucel) was approved by NMPA for the treatment of relapsed and/or refractory multiple myeloma (R/R MM) who received ≥3 lines of prior therapies containing at least one proteasome inhibitor and an immunomodulatory agent on June 30, 2023. The NDA approval was based on the data from the pivotal FUMANBA-1 study (CTR20192510, NCT05066646) conducted at multiple sites in China. According to the updated long-term follow-up data of the study published at the 2023 International Myeloma Society (IMS) Annual Meeting, as of December 31, 2022, among the 103 efficacy-evaluable patients, the overall response rate (ORR) was 96.1%, and the stringent complete response/complete response (sCR/CR) rate was 77.7%; in 91 participants without prior CAR-T therapy, ORR was 98.9%, 82.4% of patients reaching sCR/CR, and the 12-month progression-free survival (PFS) rate was 85.5%; 94.2% (97/103) of patients achieved minimal residual disease (MRD) negativity, and all sCR/CR patients achieved MRD negativity. Among the 105 participants, only one experienced ≥ Grade 3 cytokine release syndrome (CRS), with no ≥ Grade 3 immune effector cell-associated neurotoxicity syndrome (ICANS). Pharmacokinetics indicated that Equecabtagene Autoleucel persisted in vivo, with gene copy numbers detectable in 40% of participants at 24 months after infusion.

About Multiple Myeloma (MM)

Multiple myeloma (MM), a prevalent hematological malignancy, is marked by abnormal proliferation of clonal plasma cells. For treatment-naïve MM patients, common first-line treatments include multiple-drug induction therapy, consolidation therapy, and maintenance therapy, as well as autologous stem cell transplantation (ASCT). Despite initial remission, most patients will inevitably enter the relapsed or refractory stage, with no known cure to date.

According to the relevant study results published in the New England Journal of Medicine, CAR-T therapy significantly prolonged PFS and improved clinical response as compared with standard regimens in patients with relapsed/refractory multiple myeloma who had received 2-4 regimens previously[1]. In patients with lenalidomide-refractory, relapsed and refractory multiple myeloma who had received 1-3 previous therapies, the risk of disease progression or death was lower in those treated with CAR-T therapy than in those with standard care[2].

Data from Globocan indicates a rise in new MM cases in China from 20,066 in 2018 to 30,300 in 2022, and is projected to further rise to an anticipated 37,082 by 2030. Similarly, new MM cases in the United States increased from 25,962 in 2018 to 32,258 in 2022, and is projected to reach 38,000 by 2030. Worldwide, new MM cases increased from 159,985 in 2018 to 187,952 in 2022, and is projected to increase to 231,284 by 2030.

Ms. Jinhua Zhang, Founder, Chairman, and Chief Executive Officer of IASO Bio, stated, "The NMPA’s IND approval for Equecabtagene Autoleucel in second- and third-line R/RMM treatment marks a pivotal advancement in its clinical journey. Evidence suggests that earlier CAR-T therapy in R/RMM patients leads to improved survival outcome. Given the compelling efficacy and safety profile demonstrated in previous clinical studies, Equecabtagene Autoleucel is poised to address significant unmet needs in early-stage MM treatment. We are eager to commence clinical enrollment, aiming to extend the benefits of this innovative therapy to more patients experiencing early relapse."

On March 29, 2024 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, 2023 (Press release, Molecular Templates, MAR 29, 2024, View Source [SID1234641629]).

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Company Highlights

Durable single agent activity observed with MT-6402, a PD-L1 targeting direct-cell kill agent, in heavily pre-treated patients with low PD-L1+ head and neck cancer who had progressed on multiple prior therapies including checkpoint and EGFR antibodies.
Enrollment is on-going in the dose escalation study with MT-8421, a novel CTLA-4 targeting agent designed to potently deplete Tregs in the tumor environment. Unique pharmacodynamic effects demonstrating potent Treg clearance and IL-2 increases observed in patients.
Recently completed $9.5 million private placement supports continued funding of clinical stage programs.
Eric Poma, PhD., Chief Executive and Chief Scientific Officer of MTEM, stated, "We are very excited to see objective responses in heavily pre-treated, checkpoint-experienced head and neck cancer patients, a setting with high unmet medical need, with MT-6402. We are seeing evidence of monotherapy activity of long duration and in patients refractory to checkpoint therapy through a novel mechanism of tumor microenvironment remodeling. We believe these data demonstrate a new and potentially best-in-class approach to targeting the PD-1-PD-L1 axis." Dr. Poma further added, "MT-8421 is currently in dose escalation as a novel direct cell-kill approach targeting CTLA-4 to potently deplete Tregs in the tumor microenvironment. Through the first dose cohort, we are already seeing promising and differentiate pharmacodynamic effects including dramatic Treg depletion in patients."

MT-6402 (PD-L1 ETB)

MT-6402 was designed to activate T-cells through direct cell-kill of immunosuppressive PD-L1+ immune cells resulting in a remodeling of the tumor microenvironment.
In addition, MT-6402 can deliver and induce the presentation of an MHC class I CMV antigen on tumor cells for pre-existing CD8 T-cell recognition and destruction in HLA-A*02/CMV+ patients with high PD-L1 expression on their tumors.
Compelling signal of monotherapy activity with MT-6402 at higher doses in relapsed or refractory head and neck cancer (R-R HNSCC) with dose expansion study planned in low PD-L1+ R-R HNSCC patients.
10 patients with R-R HNSCC in dose escalation
Patients dosed at 63, 83 (MTD), or 100 mcg/kg; median # of prior treatments of greater than 3
2 patients currently in responses; 1 patient (63 mcg/kg) has a confirmed PR with 70% reduction in tumor volume at cycle 18 (1 cycle = 4 weeks)
1 patient (83 mcg/kg) has an uPR(37% reduction) at cycle 8 w/ reductions of 3%, 9%, and 15% across three previous cycles; the patient is on therapy in cycle 9
2 patients (one uPR and one 15% reduction) came off therapy for Gr1 hs-Trop elevation; guidelines now revised to allow patients to continue therapy despite advent of Gr1 hs-Trop elevation. In all instances, Gr1 hs-Trop elevations were asymptomatic and without evidence of cardiac changes. Similar troponin changes are observed in patients receiving checkpoint inhibitors.
No gr 4 or gr 5 drug-related toxicities were observed
Patients with responses/tumor reduction had low PD-L1
Dose expansion is on-going in patients with high PD-L1+ tumors.
MT-8421 (CTLA-4 ETB)

MT-8421, along with MT-6402, represents our unique approach to immuno-oncology based on remodeling the tumor microenvironment through the elimination of immunosuppressive cells and activation of CD8 T-cells.
MT-8421 is designed to potently destroy CTLA-4+ Tregs via enzymatic ribosome destruction but does not have activity against low CTLA-4 expressing peripheral Tregs.
Two of the three patients enrolled in the first cohort remain on study in cycle 5. Both patients show evidence of Treg clearance and T-cell activation. Enrollment is on-going in the second cohort of 48 mcg/kg for the phase I study of MT-8421.
MT-0169 (CD38 ETB)

MT-0169 is 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).
A phase 1 study in patients with relapsed or refractory multiple myeloma was closed on Dec 2023 due to slow patient enrollment in the wake of multiple new approvals in myeloma. This study enrolled 14 patients and no drug-related Grade 4 or 5 adverse events have been observed. One patient with IgA myeloma who was quad-refractory was treated at 5 mcg/kg and had a stringent Complete Response for 16 cycles (1 cycle = 4 weeks) before discontinuing treatment for progression of disease.
MTEM is evaluating plans to initiate an investigator sponsored study to evaluate MT-0169 in relapsed or refractory CD38+ AML patients.
Second Closing of July 2023 Private Placement

On March 28, 2024, the Company and certain institutional and accredited investors (the "March 2024 Purchasers") entered into an Amended and Restated July 2023 Purchase Agreement pursuant to which the Company will issue common stock, prefunded warrants, and common warrants with an aggregate purchase price of $9.5 million on amended and restated second tranche terms. The second tranche, as amended and restated, will consist of the sale and issuance of (i) 1,209,612 shares of the Company’s common stock (and, in lieu thereof, prefunded warrants to purchase 2,460,559 shares of the Company’s common stock (the "March 2024 Prefunded Warrants")) for a purchase price of $2.35 per share of the Company’s common stock (the closing price of our common stock on March 27, 2024 as reported by the Nasdaq Capital Market) and $2.349 per March 2024 Prefunded Warrant, and (ii) common stock warrants (the "March 2024 Common Warrants") to purchase up to 7,340,342 shares of the Company’s common stock (or March 2024 Prefunded Warrants in lieu thereof) at an exercise price of $2.35 per share of the Company’s common stock underlying the March 2024 Common Warrants. The March 2024 Common Warrants will be sold at a price of $0.125 per underlying share of common stock and will have a term of five years. The March 2024 Prefunded Warrants will expire when fully exercised in accordance with their terms. The March 2024 Prefunded Warrants and March 2024 Common Warrants may not be exercised if the aggregate number of shares of our common stock beneficially owned by the holder thereof immediately following such exercise would exceed a specified beneficial ownership limitation (4.99%/9.99%/19.99%); provided, however, that a holder may increase or decrease the beneficial ownership limitation by giving 61 days’ notice to the Company, but not to any percentage in excess of 19.99%. The Amended and Restated July 2023 Purchase Agreement contains customary representations and warranties and agreements of the Company and the Purchasers and customary indemnification rights and obligations of the parties. The second tranche will include gross proceeds of approximately $9.5 million and net proceeds, following the payment of related offering expenses, of approximately $8.9 million.

Key Milestones for 2024

Clinical data on MT-6402 expansion cohorts in low and high PD-L1+ HNSCC patients
Clinical data from dose escalation study for MT-8421 Treg depleting agent in solid tumors
Bristol-Myers Squibb Collaboration Agreement

On March 13, 2024, Bristol-Myers Squibb notified the Company that following a corporate portfolio prioritization process, it does not intend to continue the research collaboration it entered into with the Company pursuant to the BMS Collaboration Agreement and would be terminating the BMS Collaboration Agreement in its entirety. The termination will be effective on June 13, 2024, or 90 days following the Company’s receipt of Bristol-Myers Squibb’s written notice of termination. MTEM plans to reduce costs related to the Collaboration Agreement.

Conferences

MTEM will present an abstract, "First-in-human, dose escalation and expansion study of MT-6402, a novel engineered toxin body (ETB) targeting PD-L1, in patients with PD-L1 expressing relapsed/refractory advanced solid tumors: Interim Data", Tuesday, April 9, 2024, 9am – 12:30pm ET (Section 48, Poster #19, Abstract #CT191), at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting taking place in San Diego, CA.

Financial Results

The net loss attributable to common shareholders for the fourth quarter of 2023 was $3.9 million, or $0.73 per basic and diluted share. This compares with a net loss attributable to common shareholders of $22.0 million, or $5.87 per basic and diluted share, for the same period in 2022.

Revenues for the fourth quarter of 2023 were $7.0 million, compared to $2.6 million for the same period in 2022. Revenues for the fourth quarter of 2023 were comprised of revenues from collaborative research and development agreements with Bristol-Myers Squibb and grant revenue.

Total research and development expenses for the fourth quarter of 2023 were $8.8 million, compared with $17.6 million for the same period in 2022. Total general and administrative expenses for the fourth quarter of 2023 were $3.6 million, compared with $6.1 million for the same period in 2022.

As of December 31, 2023, MTEM’s unrestricted cash and cash equivalents totaled $11.5 million. MTEM anticipates a cash runway into the second quarter of 2024. Following the completion of the recent Second Closing of the July 2023 Private Placement, the Company anticipates that cash runway will extend to the end of the fourth quarter 2024.

For more details on MTEM’s financial results for 2023, refer to Form 10-K filed with the SEC.

Molecular Templates, Inc.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except share and per share data)
(unaudited)

Three Months Ended
December 31, Year Ended
December 31,
2023 2022 2023 2022
Research and development revenue $ 6,639 $ 2,611 $ 52,625 $ 19,754
Grant revenue 377 — 4,681 —
Total revenue 7,016 2,611 57,306 19,754
Operating expenses:
Research and development 8,796 17,590 48,875 82,425
General and administrative 3,591 6,080 18,897 26,200
Total operating expenses 12,387 23,670 67,772 108,625
Loss from operations 5,371 21,059 10,466 88,871
Interest and other income, net 178 425 1,208 988
Interest and other expense, net (39 ) (1,351 ) (2,654 ) (4,716 )
Gain on extinguishment of debt — — 1,795 —
Change in valuation of contingent value right 1,273 — 2,457 —
Loss on disposal of property and equipment — (37 ) (475 ) (66 )
Loss before provision (benefit) for income taxes 3,959 22,022 8,135 92,665
Provision (benefit) for income taxes (11 ) 27 (11 ) 53
Net loss attributable to common shareholders $ 3,948 $ 22,049 $ 8,124 $ 92,718
Net loss per share attributable to common shareholders:
Basic and diluted $ 0.73 $ 5.87 $ 1.80 $ 24.69
Weighted average number of shares used in net loss per share calculations:
Basic and diluted 5,374,268 3,756,711 4,501,206 3,755,564

Molecular Templates, Inc.
CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands, except share and per share data)

December 31,
2023
December 31,
2022
ASSETS
Current assets:
Cash and cash equivalents $ 11,523 $ 32,190
Marketable securities, current — 28,859
Prepaid expenses 2,195 3,459
Grants revenue receivable 250 —
Other current assets 2,804 3,790
Total current assets 16,772 68,298
Operating lease right-of-use assets 9,161 11,132
Property and equipment, net 7,393 14,632
Other assets 2,057 3,486
Total assets $ 35,383 $ 97,548
LIABILITIES AND STOCKHOLDERS’ EQUITY/(DEFICIT)
Current liabilities:
Accounts payable $ 1,523 $ 504
Accrued liabilities 4,279 8,823
Deferred revenue, current 9,031 45,573
Other current liabilities 2,488 2,182
Total current liabilities 17,321 57,082
Deferred revenue, long-term — 5,904
Long-term debt, net of current portion — 36,168
Operating lease liabilities, long term portion 9,742 12,231
Contingent value right liability 2,702 —
Other liabilities 1,406 1,295
Total liabilities 31,171 112,680
Commitments and contingencies
Stockholders’ equity/(deficit)
Preferred stock, $0.001 par value per share:
Authorized: 2,000,000 shares as of December 31, 2023 and 2022; Issued and outstanding: 250 shares as of December 31, 2023 and 2022 — —
Common stock, $0.001 par value per share:
Authorized: 150,000,000 shares as of December 31, 2023 and 2022; Issued and outstanding: 5,374,268 shares as of December 31, 2023 and 3,756,711 shares as of December 31, 20221 5 4
Additional paid-in capital1 457,099 429,698
Accumulated other comprehensive loss — (66 )
Accumulated deficit (452,892 ) (444,768 )
Total stockholders’ equity/(deficit) 4,212 (15,132 )
Total liabilities and stockholders’ equity/(deficit) $ 35,383 $ 97,548

1. Prior period amounts have been retrospectively adjusted for the 1-for-15 reverse stock split that was effective August 11, 2023.

On March 29, 2024 Vincerx Pharma, Inc. (Nasdaq: VINC), a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a corporate update (Press release, Vincerx Pharma, MAR 29, 2024, View Source [SID1234641627]).

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"The last calendar year was pivotal for Vincerx," said Ahmed Hamdy, M.D., Chief Executive Officer. "Having progressed three clinical programs, including VIP236 and VIP943, both developed with our VersAptxTM platform, and enitociclib, we firmly established ourselves as a clinical-stage cancer therapeutics company with novel product candidates that aim to improve safety and efficacy over traditional chemotherapy."

Raquel Izumi, Ph.D., Chief Operations Officer, added, "VIP236, our first-in-class SMDC, is in a Phase 1 dose-escalation trial for advanced and metastatic solid tumors. To date, we have dosed 20 patients across two dosing schedules and results from the once every 3-week dosing schedule continue to show a strong safety profile with dose-dependent clinical activity. We are excited to share more details regarding the preliminary Phase 1 data during the 2024 AACR (Free AACR Whitepaper) Annual Meeting."

Dr. Izumi continued, "VIP943, our best-in-class anti-CD123 ADC, is in a Phase 1 dose-escalation trial in hematologic malignancies. Enrollment in the third cohort is underway with a total of 9 patients dosed. Preliminary pharmacokinetic data from the first two cohorts show very little payload in circulation, which aligns with the favorable safety profile observed in nonhuman primates in our preclinical studies. We look forward to sharing pharmacokinetic data for VIP943 during AACR (Free AACR Whitepaper) and more details regarding the preliminary Phase 1 data on or around EHA (Free EHA Whitepaper). Enitociclib, our highly selective CDK9 inhibitor, in a Phase 1 dose-escalation study with the National Institutes of Health (NIH), has signaled encouraging efficacy in Phase 1 combination studies in peripheral T-cell lymphoma (PTCL) and double-hit B-cell lymphoma (DLBCL). Earlier this year, we reported partial responses at doses below expected efficacy levels, highlighting the drugs synergistic potential with other treatments."

Dr. Hamdy concluded, "We entered 2024 with strong momentum and remain focused on aggressively advancing our programs and maximizing the value of our next-generation VersAptx platform."

FOURTH QUARTER AND FULL YEAR 2023 CLINICAL PROGRAM HIGHLIGHTS

VersAptx Platform

VersAptx is Vincerx’s versatile and adaptable, next-generation bioconjugation platform. The modular nature of this platform enables the combination of different targeting, linker, and payload technologies to develop bespoke bioconjugates to address different cancer biologies.
Recent preclinical data demonstrated the ability of our legumain linker + KSPi payload with CellTrapper effector chemistry to enhance the potency of TRODELVY and ENHERTU, two marketed ADCs, by conjugating TRODELVY’s TROP2 and ENHERTU’s HER2 antibodies with our effector chemistry. The results of this study demonstrated a significant improvement in the potency of both drugs, with TRODELVY potency amplified by a factor of 20 and ENHERTU potency by a factor of 8.
Vincerx published a manuscript in Frontiers in Pharmacology titled, "Neutrophil elastase as a versatile cleavage enzyme for activation of αvβ3 integrin-targeted small molecule drug conjugates with different payload classes in the tumor microenvironment."
Vincerx presented a preclinical poster at the 2023 AACR (Free AACR Whitepaper) Annual Meeting demonstrating the promise of VIP924, a first-in-class CXCR5-targeted ADC from the VersAptx platform.
VIP236

VIP236 is a αVβ3 SMDC conjugated to an optimized camptothecin (CPT) from the VersAptx platform. VIP236 is a first-in-class product candidate designed to deliver its optimized CPT payload directly to tumor tissues to overcome the chemotherapy-related side effects and transporter liabilities of this well-established class of anticancer drugs. Preclinical studies have shown 11 times more optimized CPT is delivered to the cancerous tissues than found circulating in the blood. Additionally, the active component of VIP236 is designed to bypass cancer resistance mechanisms.
The favorable characteristics of VIP236, including improved linker attachment, stable solubility, and tumor-specific payload release, were featured in a peer-reviewed publication titled, "Unleashing the Potential of Camptothecin: Exploring Innovative Strategies for Structural Modification and Therapeutic Advancements," by Zheng Chen in the March 14, 2024 issue of Journal of Medicinal Chemistry.
To date, the VIP236 Phase 1 dose-escalation trial (NTC05371054) has enrolled 20 patients with advanced or metastatic cancer unresponsive to standard therapies.
Vincerx will present more details around the preliminary Phase 1 data at the upcoming 2024 AACR (Free AACR Whitepaper) Annual Meeting, accompanied by a virtual investor event to review the data and provide a pipeline update on April 8 at 2:00 PM PT. The event can be accessed through the Investors Page on the Vincerx website.
VIP943

VIP943 is a novel CD123-targeted antibody-drug conjugate (ADC) from the VersAptx platform.
In August 2023, Vincerx received IND clearance for a Phase 1 dose-escalation trial of VIP943 in relapsed/refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and B-cell acute lymphoblastic leukemia (B-ALL) (NCT06034275).
In September 2023, Vincerx announced the dosing of its first patient in that study.
Enrollment in the third cohort is underway, with a total of 9 patients dosed. Preliminary pharmacokinetic results continue to show very little payload circulating in the blood, validating the favorable safety profile observed in nonhuman primates in preclinical studies.
Vincerx will present more details regarding the preliminary Phase 1 data for VIP943 on or around the 2024 EHA (Free EHA Whitepaper) Annual Meeting.

Enitociclib

Enitociclib is a highly selective CDK9 inhibitor designed to block the activation of RNA polymerase II, leading to the reduction of oncogenes MYC and MCL1.
In 2023, Vincerx presented preclinical data supporting the continued advancement of enitociclib at multiple medical congresses. Vincerx also published a manuscript titled, "Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription" in Cancer Research Communications, an AACR (Free AACR Whitepaper) journal.
Enitociclib is currently in a Phase 1 dose-escalation trial (NTC05371054) evaluating the combination of enitociclib, venetoclax, and prednisone in DLBCL and PTCL. This trial is being conducted in collaboration with the NIH.
Earlier this year, Vincerx announced that 2 out of 3 patients with PTCL had a partial response (PR). The first patient saw a 91% reduction in their tumor burden, while the second patient saw an 86% reduction in pulmonary lesions and resolution of skin lesions. In addition, 1 out of 2 patients with DH-DLBCL had a PR after one cycle of treatment, seeing an 80% reduction in tumor burden. These responses occurred at doses below expected efficacy levels.
VIP924

VIP924 is a first-in-class CXCR5-targeted ADC from the VersAptx platform.
Vincerx presented preclinical data at the 2023 AACR (Free AACR Whitepaper) Annual Meeting demonstrating significant activity in patient-derived xenograft (PDX) lymphoma mouse models.
Vincerx shared preclinical data at the 2023 ASH (Free ASH Whitepaper) Annual Meeting showing superior activity and safety compared with commercially available B-cell targeted ADCs.
IND application anticipated in late 2025 or early 2026, pending funding.
FOURTH QUARTER AND FULL YEAR 2023 FINANCIAL RESULTS

Vincerx had $12.8 million in cash and cash equivalents as of December 31, 2023, as compared to $52.5 million in cash, cash equivalents and marketable securities as of December 31, 2022. Based on its current business plans and assumptions, Vincerx believes its available capital will be sufficient to meet its operating requirements into early third quarter of 2024.
Research and development (R&D) expenses for the fourth quarter and full year 2023 were $3.7 million and $29.0 million, respectively, as compared to $11.5 million and $49.8 million, respectively, for each of the same periods in 2022. The year over year decrease of approximately $20.9 million is primarily the result of decreases in third party service and supplier expenses, including manufacturing services associated with our ADC program of approximately $9.7 million and clinical services of approximately $2.6 million, as well as decreases in expenses related to headcount, including declines in stock-based compensation expense of approximately $3.3 million and employee salaries of approximately $3.1 million as a result of our headcount reduction in June 2022.
General and administrative (G&A) expenses for the fourth quarter and full year 2023 were $1.8 million and $13.6 million, respectively, as compared to $4.0 million and $18.9 million for the same periods in 2022. The year over year decrease of approximately $5.2 million was primarily driven by decreases in stock-based compensation expense of $2.8 million, professional services of $1.4 million, and a decrease in expenses related to headcount of $0.7 million.
For the fourth quarter and full year 2023, Vincerx reported a net loss of $4.9 million, or $0.23 per share, and a net loss of $40.2 million, or $1.89 per share, respectively. For the fourth quarter and full year 2022, Vincerx reported a net loss of $13.8 million, or $0.65 per share, and a net loss of $63.0 million, or $3.00 per share, respectively.