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.

On March 29, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a platform-driven, clinical-stage biotechnology company transforming the discovery and development of novel antibody-based therapies, reported financial results for the full year 2023 and provided corporate updates (Press release, Adagene, MAR 29, 2024, View Source [SID1234641626]).

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"The SAFEbody precision masking technology platform remains at the core of our value proposition given its ability to enhance next generation antibody-based therapies that span modalities, including bispecific T-cell engagers and antibody-drug conjugates, both areas where a wider therapeutic index is needed to fully address solid tumors," said Peter Luo, Ph.D., Chairman, CEO and President of R&D at Adagene.

He continued, "Turning to our clinical pipeline, we remain steadfast in our belief that anti-CTLA-4 therapy can be reimagined as a cornerstone of cancer care by enabling higher, more frequent and repeated doses in combination with anti-PD-1 and other therapies. With our SAFEbody platform, we have a 30-fold improved therapeutic index for ADG126 and a mechanism enabling CTLA-4 mediated intratumoral Treg depletion. We are taking anti-CTLA-4 therapy to a new level unleashing this proven immunotherapy where safety has limited its therapeutic potential."

"In particular, our new loading dose regimen in late-stage MSS CRC patients enables our masked anti-CTLA-4 therapy to reach a high initial concentration, close to the steady state of activated species within the tumor tissue to immediately engage the CTLA-4 pathway and stop the tumor from aggressive growth. This loading dose strategy, together with repeated maintenance doses at 10 mg/kg showing limited treatment-related grade 3 and no higher toxicities with minimal late-onset toxicities for ADG126, is expected to engage the CTLA-4 target consistently, thereby maintaining and sustaining clinical benefit, via both the initial response rate and prolonged survival benefit. We look forward to reporting more clinical results for the ADG126 combination dose expansion in MSS CRC later this year."

PIPELINE HIGHLIGHTS

Phase 1b/2 data for ADG126, a masked anti-CTLA-4 SAFEbody targeting a unique epitope of CTLA-4 on regulatory T cells (Tregs) in tumor tissue as driven by the fundamental biology of CTLA-4, showed a potential best-in-class profile in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab)*, in MSS CRC, PD-1 experienced and PD-L1 low tumors:
Results presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Symposium from dose escalation and dose expansion cohorts of ADG126 in combination with pembrolizumab (200 mg/Q3W) demonstrated a differentiated safety profile for ADG126 at doses from 6 mg/kg to 10 mg/kg in heavily pre-treated advanced/metastatic patients (N=46):
Limited dose-dependent toxicities were observed.
Grade 3 TRAEs occurred in 5/46 patients (10.8%), with no Grade 4 or 5 TRAEs and a discontinuation rate of 6.5% (3/46).
In dose escalation across tumor types, two partial confirmed responses (PRs) were observed among the three patients treated with ADG126 10 mg/kg Q3W, which triggered expansion cohorts at this dosing regimen. One of the patients had PD-1 refractory cervical cancer and the other had endometrial cancer. Both confirmed PRs are sustained after more than one year with repeat dosing while maintaining robust safety profiles.
In dose expansion of patients with MSS CRC, 12 evaluable patients without liver metastases were treated at the active, potent dose of 10 mg/kg Q3W:
Two confirmed PRs were observed in nine of these patients without peritoneal and liver metastases, resulting in an overall response rate of 22% in this subset.
An additional seven of these nine patients experienced stable disease (SD) for an overall disease control rate of 100% (2 PRs and 7 SD).
Observation of these clinical activities triggered further expansion into the second stage of the Simon’s 2-stage design for this dose level.
In a preliminary progression-free survival (PFS) analysis of those MSS CRC patients free of liver and peritoneal metastasis, a median PFS of seven months was observed in those treated with ADG126 10 mg/kg at two dosing frequencies pooled together [every three weeks (n=9) and every six weeks (n=6)]. The durable clinical activity of ADG126 in combination with pembrolizumab will continue to be evaluated as a larger cohort of subjects becomes evaluable at the 10 mg/kg Q3W dose level.
Following the ASCO (Free ASCO Whitepaper) GI Symposium, Adagene announced progress and expansion of the ADG126 clinical program, which increases the ongoing phase 2 dose expansion in MSS CRC to over 50 patients. Updates included:
Enrollment of 12 additional patients in the second stage of the Simon’s 2-stage design was completed in the fourth quarter of 2023 for the ongoing phase 2 dose expansion cohort evaluating ADG126 10 mg/kg Q3W in combination with pembrolizumab in MSS CRC. These Part 2 results will supplement data from Part 1 of the dose expansion in MSS CRC as recently presented at the 2024 ASCO (Free ASCO Whitepaper) GI Symposium.
Given the ADG126 safety profile, evaluation of the 20 mg/kg loading dose regimen has been initiated in combination with pembrolizumab in patients with advanced/metastatic cancer. Pending outcome of the ongoing safety evaluation, the company plans to evaluate the efficacy profile of the loading dose regimen in expansion cohorts, followed by maintenance with ADG126 10 mg/kg Q3W in combination with pembrolizumab at sites in the US and Asia Pacific.
Clearance received from China’s Center for Drug Evaluation to initiate clinical evaluation of ADG126 in combination with pembrolizumab. This enables the company to broaden its dose expansion cohorts for MSS CRC at selected dosing regimens, and potentially in other tumor types, in its clinical trial collaboration and supply agreement with Merck.
Additionally, the company recently initiated dosing of a small number of patients with advanced/metastatic cancers at 30 mg/kg ADG126 monotherapy Q3W in China to define the potential maximum tolerated dose of ADG126 monotherapy.
Phase 1b/2 data for ADG116, an unmasked anti-CTLA-4 NEObody targeting a unique epitope, showed a favorable safety profile and clinical responses, both in monotherapy and in combination with anti-PD-1:
ADG116 monotherapy has demonstrated a favorable safety profile at doses up to 15 mg/kg (N=59) and an overall response rate (ORR) of 13% (3/23 evaluable), including confirmed and durable PRs in multiple tumor types.
In combination with anti-PD-1 therapy, ADG116 (3 mg/kg Q6W) (N=22) showed a manageable safety profile and an encouraging efficacy profile in dose escalation. Clinical responses from the combination cohorts include a complete response (CR) sustained for nearly two years in a head and neck squamous cell carcinoma (HNSCC) patient dosed with repeat cycles of ADG116 3 mg/kg (initially every three weeks, then every six weeks) plus toripalimab (ORR = 20%; 1/5 evaluable). An initial PR was also observed in a patient with MSS CRC dosed with repeat cycles of ADG116 3 mg/kg every six weeks plus toripalimab, further demonstrating the potential clinical benefit associated with targeting a unique epitope of CTLA-4 and the essential effects of Treg depletion.
ADG116 is clinically active and ready to advance into further clinical development as resources allow.
Phase 1 evaluation is ongoing for ADG206, a masked, IgG1 FC-enhanced anti-CD137 POWERbody in patients with advanced/metastatic tumors:
Adagene has enrolled 10 patients in an ongoing phase 1 trial of ADG206 to evaluate safety, efficacy and tolerability profiles for this next generation anti-CD137 candidate. Dose escalation continues with a cohort ongoing at 3 mg/kg Q3W. No maximum tolerated dose (MTD) has yet been reached.
Preclinical data demonstrated that ADG206 was well tolerated and had robust anti-tumor activity as a single agent in multiple tumor models, with 4-fold stronger anti-CD137 agonistic activity of its activated form than a benchmark antibody (urelumab analog) that displayed dose-dependent liver toxicity with an MTD of 0.1 mg/kg Q3W.
ADG206 is the company’s first SAFEbody with Fc enhancement, called a POWERbody, to advance into clinic. ADG206 combines SAFEbody precision masking, Fc enhancement and targeting of a unique epitope to solve the safety and efficacy challenges of anti-CD137 therapies, reflecting versatility of Adagene’s dynamic antibody discovery and masking platform.
COLLABORATIONS

Exelixis: In June 2023, Adagene received a US$3.0 million milestone payment from Exelixis for the successful nomination of lead SAFEbody candidates for the second collaboration program under a technology licensing agreement to develop novel masked antibody-drug conjugate candidates.
Sanofi: Adagene and Sanofi are collaborating to develop both bispecific and monoclonal SAFEbody antibody candidates, preparing preclinical candidates using Adagene’s SAFEbody precision masking technology for future development and commercialization by Sanofi. The collaboration announced in March 2022 included an upfront payment of US$17.5 million for the initial two programs, an option fee for two additional programs, potential milestone payments of up to US$2.5 billion, and tiered royalties.
Roche: Roche is sponsoring and conducting a phase 1b/2 multi-national trial to evaluate ADG126 in a triple combination with atezolizumab and bevacizumab in first-line hepatocellular carcinoma (HCC). Adagene retains global development and commercialization rights to ADG126.
CHANGE OF BOARD OF DIRECTORS

The following changes to Adagene’s Board of Directors will be effective upon the filing of its 2023 annual report on Form 20-F ("2023 Annual Report"), unless otherwise noted:

Dr. Ulf Grawunder will join the Board of Directors (the "Board") as an independent director and serves as a member of Audit Committee and Strategy Committee of the Board. Dr. Grawunder is an experienced Swiss/German life-science entrepreneur with over 20 years of experience in the therapeutic antibody development industry.
Dr. Zhu Li, currently an independent director, will serve as a member of Compensation Committee of the Board.
Term of Mr. Andy (Yiu Leung) Cheung, Dr. Mervyn Turner and Mr. Man Kin (Raymond) Tam will be extended.
Dr. Min Li, currently an independent director and a member of Audit Committee, Compensation Committee and Nominating and Corporate Governance Committee, and Ms. Yan Li, Senior Vice President of Bioinformatics and Information Technology and currently a member of the Board, will resign as directors of the Board and membership of the various committees, as applicable, due to person reasons. Ms. Yan Li’s resignation from the board will be effective on June 15, 2024, after which she will continue to serve as an observer to the Board. Each of Dr. Min Li and Ms. Yan Li confirmed that he or she has no disagreement with the Board, and there is no other matter relating to his or her resignation that needs to be brought to the attention of the shareholders of the company.
The Board would like to take this opportunity to express their sincere gratitude to Dr. Min Li and Ms. Yan Li for their valuable contributions to the Board during their tenure. Background of the newly appointed directors and their terms are detailed in the 2023 Annual Report.

2024 MILESTONES & CASH RUNWAY INTO 2026

Consistent with ongoing initiatives to prudently manage its cash balance, Adagene expects its current cash balance to fund activities into 2026, with the following milestones:

Data from the ongoing phase 1b/2 clinical trial of ADG126 in combination with pembrolizumab, including dose expansion cohorts in MSS CRC, are anticipated throughout 2024:
Follow up of Part 1 evaluable patients at 10 mg/kg Q3W (n=12) and 10 mg/kg Q6W (n=10)
Data from Part 2 patients at 10 mg/kg Q3W (n=12)
Evaluation of 20 mg/kg loading doses for Project Optimus requirements:
Safety data with repeat doses
Dose expansion in MSS CRC (n~10)
Additional patients in China (n≥10)
Additional technology licensing agreement(s) and/or milestone(s).
FINANCIAL HIGHLIGHTS

Cash and Cash Equivalents
Cash and cash equivalents were US$109.9 million as of December 31, 2023, compared to US$143.8 million as of December 31, 2022. Total borrowings from commercial banks in China (denominated in RMB) decreased to US$21.9 million as of December 31, 2023 from US$27.8 million as of December 31, 2022. The associated loan proceeds were primarily used to pay for the company’s R&D activities in China.

Net Revenue:
Net revenue was US$18.1 million for the year ended December 31, 2023, compared to US$9.3 million in 2022. The increase of approximately 95% reflects net revenue recognized upon fulfillment of certain performance obligations associated with the collaboration and technology licensing agreements with Exelixis and Sanofi, respectively. Net revenue also included a milestone payment of US$3.0 million from Exelixis received in June 2023.

Research and Development (R&D) Expenses:
R&D expenses were US$36.6 million for the year ended December 31, 2023, compared to US$81.3 million in 2022. The decrease of approximately 55% in R&D expenses reflects clinical focus on and prioritization of the company’s masked, anti-CTLA-4 SAFEbody ADG126.

Administrative Expenses:
Administrative expenses were US$8.7 million for the year ended December 31, 2023, compared to US$11.9 million in 2022. The decrease was due to both a reduction in personnel and in office-related expenses as a result of cost-control measures.

Other Operating Income, Net:
Other operating income, net was US$3.5 million for the year ended December 31, 2023. Other operating income, net included a one-time compensation payment from a contract manufacturer for a preclinical-related outsourcing arrangement.

Net Loss:
Net loss attributable to Adagene Inc.’s shareholders was US$18.9 million for the year ended December 31, 2023, compared to US$80.0 million in 2022.

Ordinary Shares Outstanding:
As of December 31, 2023, there were 55,145,839 ordinary shares issued and outstanding. Each American depository share, or ADS, represents one and one quarter (1.25) ordinary shares of the company.

Non-GAAP Net Loss:
Non-GAAP net loss, which is defined as net loss attributable to ordinary shareholders for the period after excluding share-based compensation expenses, was US$11.7 million for the year ended December 31, 2023, compared to US$69.5 million in 2022. Please refer to the section in this press release titled "Reconciliation of GAAP and Non-GAAP Results" for details.