On August 12, 2024 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported its novel Nectin-4 targeting ADC (R&D code: 9MW2821) has been granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the treatment of locally advanced or metastatic urothelial carcinoma that has failed previous platinum-based chemotherapy and PD-(L)1 inhibitor therapy (Press release, Mabwell Biotech, AUG 12, 2024, View Source [SID1234645752]).

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The designation as a breakthrough therapy is aimed at expediting the development process of drug candidates for serious diseases, with the drug candidates included having demonstrated significant efficacy or safety advantages compared to existing therapies in early clinical trials.

For drug candidates included in the breakthrough therapy list, CDE will prioritize the allocation of resources to facilitate communication and provide guidance to promote drug development, which will benefit the further advancement of the clinical development progress and the speed of market review and approval. This will help to expedite the development process of 9MW2821 and meet the unmet clinical needs of Chinese patients.

About 9MW2821

9MW2821 is the first site-specific conjugated novel Nectin-4 targeting ADC developed by Mabwell using ADC platform, and is the first drug candidate to enter clinical study among the Nectin-4-targeting ADCs developed by Chinese companies, and also the first therapeutic drug candidate targeting Nectin-4 in the world to reveal clinical efficacy data of cervical cancer (CC), esophageal cancer (EC) and breast cancer. In 2024, 9MW2821 has been granted Fast Track Designation by FDA for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC), recurrent or metastatic CC progressed on or following prior treatment with a platinum-based chemotherapy regimen, and locally advanced or metastatic Nectin-4 positive triple-negative breast cancer (TNBC); 9MW2821 has been granted Orphan Drug Designation by FDA for the treatment of EC, and also Breakthrough Therapy Designation by China NMPA.

9MW2821 achieves site-specific modification of antibody through proprietary conjugation technology linkers and optimized ADC conjugation process. After injection, 9MW2821 can specifically bind to Nectin-4 on the cell membrane surface, be internalized and release cytotoxic drug, and induce the apoptosis of tumor cells.

On August 12, 2024 Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on the development of first-in-class and best-in-class targeted oncology therapies, reported financial results for the second quarter ended June 30, 2024, and provided a business update (Press release, Immunome, AUG 12, 2024, View Source [SID1234645730]).

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"Immunome is focused on establishing and developing a broad pipeline of differentiated oncology therapies. We continue to advance work required to prepare AL102 for regulatory submissions, and we are moving towards submitting INDs for IM-1021 and IM-3050," said Clay B. Siegall, Ph.D., President and Chief Executive Officer. "These programs are supported by an expanding team of drug developers, including leaders who previously contributed to the successful development and commercialization of ADCs and small molecules."

Dr. Siegall continued, "In addition to our clinical pipeline, we have identified multiple promising ADC targets, all of which offer first-in-class potential. We believe that cost-effective business development efforts combined with focused research can accelerate the expansion of our pipeline and that rigorous science provides the foundation for transformative cancer therapies."

Pipeline Highlights

Full enrollment for the Phase 3 RINGSIDE Part B study of AL102 for the treatment of desmoid tumors was completed in February 2024, and Immunome continues to expect to report topline data for RINGSIDE Part B in the second half of 2025. In parallel, Immunome is performing additional manufacturing and pharmacology work required to support a new drug application filing for AL102.

Immunome also anticipates submitting INDs for IM-1021 and IM-3050 in the first quarter of 2025, as previously disclosed.

These programs are complemented by robust discovery efforts centered on next-generation ADCs and active business development activity, including recent transactions with Atreca, Nectin Therapeutics, Bluefin Biomedicine, and OncoResponse intended to expand Immunome’s ADC toolbox.

Second Quarter 2024 Financial Results

· As of June 30, 2024, cash, cash equivalents and marketable securities totaled $278.4 million. Immunome’s current cash runway is expected to extend into 2026.

· Research and development expenses for the quarter ended June 30, 2024 were $29.1 million, including stock-based compensation costs of $1.0 million.
· In-process research and development expenses for the quarter ended June 30th, 2024 were $6.3 million. These expenses were related to Immunome’s business development activity.
· General and administrative expenses for the quarter ended June 30, 2024 were $7.0 million, including stock-based compensation expense of $2.2 million.
· Immunome reported a net loss of $36.1 million for the quarter ended June 30, 2024.

On August 12, 2024 Ascentage Pharma (6855.HK), a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing both first- and best-in-class therapies for malignancies, reported that it has been cleared by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) to initiate a registrational Phase III study of lisaftoclax (APG-2575), one of the company’s key drug candidates, in combination with azacitidine (AZA) for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS) (Press release, Ascentage Pharma, AUG 12, 2024, View Source [SID1234645753]). This clears the fourth registrational Phase III study of lisaftoclax, marking another major milestone in the clinical development of the drug.

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This study (GLORA-4) is a multi-center, randomized, double-blind, pivotal registrational Phase III trial to evaluate the efficacy of lisaftoclax in combination with AZA in newly-diagnosed adult patients with higher-risk MDS.

As a heterogeneous myeloid clonal disease originating from hematopoietic stem cells, MDS commonly occurs in older population with a median age of onset of 70 years and an incidence rate that increases with age.1 MDS is characterized by the abnormal growth of myeloid cells. Its clinical manifestations include hematopoietic failure, refractory cytopenia, and the propensity for high-risk patients to progress to acute myeloid leukemia (AML). Data show that approximately 10% of low-risk patients and 50% of high-risk patients with MDS would progress to AML and thereafter face a dismal prognosis.2

At present, there are limited treatment options for patients with MDS and the treatment outcome for most patients remains relatively poor. Demethylation agents (AZA or decitabine) are the current standard first-line treatment for patients with higher-risk MDS. Studies showed that compared to conventional care regimens, monotherapy with AZA can improve the overall survival of patients with MDS.3 Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only available curative treatment for MDS. However, the complex characteristics of MDS and the old ages of patients have resulted in the intolerability of chemotherapies that limited the rate of transplantation, and the high rate of transplantation-associated mortality among patients with MDS. The low survival rate of patients with higher-risk MDS underscores an urgent unmet medical need for novel therapies and medicines that can offer higher efficacies.

Lisaftoclax is a novel, orally administered Bcl-2 selective inhibitor being developed by Ascentage Pharma to treat the patients with malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. Lisaftoclax is expected to be the first Bcl-2 inhibitor for which an NDA will be filed for chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) in China and the second anywhere globally that has demonstrated clinical activity for the treatment of patients with CLL and entered pivotal registrational studies. In published clinical results released at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the drug candidate lisaftoclax has demonstrated clinical benefit and tolerability in patients with higher-risk MDS.4

"There is considerable unmet clinical need for patients with MDS. Lisaftoclax, a Bcl-2 inhibitor, has already shown promising clinical benefit and tolerability in early studies in patients with MDS," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We are very encouraged by this approval for initiation of the registrational Phase III study in the first-line treatment of patients with higher-risk MDS, as it clears the way for the fourth registrational Phase III study of lisaftoclax. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will actively press ahead with the clinical trials of lisaftoclax for the benefit of more patients."

*Lisaftoclax is an investigational drug that has not been approved in any country or region.

On August 12, 2024 Biogen Inc. (the "Company") reported to have entered into a credit agreement with Bank of America, N.A., as Administrative Agent, Swing Line Lender and the L/C Issuer, and the lenders party thereto (the "Credit Agreement") (Filing, 8-K, Biogen, AUG 12, 2024, View Source [SID1234645889]). The Credit Agreement provides for a $1.5 billion five-year unsecured, revolving credit facility (the "Revolving Credit Facility"). The Revolving Credit Facility includes borrowing capacity in the form of letters of credit of up to $25.0 million and $20.0 million in swing line loans.

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Borrowings under the Revolving Credit Facility are available for general corporate purposes. No proceeds from the Revolving Credit Facility were drawn down as of the closing date of the Credit Agreement.

Revolving loans under the Credit Agreement (other than swing line loans) will bear interest at rate per annum equal to (i) Term SOFR, with respect to revolving loans denominated in dollars, (ii) EURIBOR, with respect to revolving loans denominated in euros, (iii) TIBOR, with respect to revolving loans denominated in yen, (iv) SONIA, with respect to revolving loans denominated in sterling, and (v) SARON, with respect to revolving loans denominated in Swiss francs, in each case, subject to a floor of 0.00% per annum, plus an applicable margin ranging from 0.625% to 1.375% depending on the ratings of the Company’s non-credit enhanced, senior unsecured long-term debt, as determined by either Standard & Poor’s or Moody’s (the "Debt Ratings") or, at the Company’s option, with respect to revolving loans denominated in dollars, a Base Rate equal to the higher of (i) the Bank of America prime rate, (ii) the Federal Funds Rate plus 0.50% and (iii) Term SOFR plus 1.00%, subject to a floor of 0.00% per annum (the "Base Rate"), plus an applicable margin ranging from 0.000% to 0.375% based on the Company’s Debt Ratings. Swing line loans will bear interest at the Base Rate plus the applicable margin for Base Rate loans.

In addition to paying interest on any outstanding principal under the Revolving Credit Facility, the Company will pay (i) a commitment fee in respect of the unutilized commitments thereunder and (ii) customary letter of credit fees and agency fees. The commitment fees range from 0.050% to 0.150% per annum based on the Company’s Debt Ratings.

The Revolving Credit Facility will terminate and all amounts outstanding thereunder are due and payable five years after the closing date, subject to certain extension options as set forth in the Credit Agreement. Under the Revolving Credit Facility, voluntary prepayments are permitted, in whole or in part, without premium or penalty, other than customary breakage costs. The Revolving Credit Facility requires quarterly interest payments or, in the case of borrowings that bear interest by reference to a term rate, at the end of the interest period therefor, with the principal due on the maturity date.

The Credit Agreement contains customary representations and warranties, affirmative and negative covenants and events of default. The Credit Agreement also includes a financial covenant requiring the Company to maintain, measured as of the end of each fiscal quarter, a maximum consolidated leverage ratio of 3.75 to 1.0 (which may be temporarily increased to 4.25 to 1.0 upon the election of the Company as a result of a material acquisition, subject to customary limitations).

A copy of the Credit Agreement is attached hereto as Exhibit 10.1 and is incorporated herein by reference. The description of the Credit Agreement is a summary only and is qualified in its entirety by the terms of the Credit Agreement.

On August 12, 2024 IN8bio, Inc. (Nasdaq: INAB), a leading clinical-stage biopharmaceutical company developing innovative gamma-delta T cell therapies for cancer, reported updated positive clinical data from both of the Company’s Phase 1 investigator-sponsored trials of INB-100 for hematological malignancies and INB-200 for GBM (Press release, In8bio, AUG 12, 2024, View Source [SID1234645731]). The Company has also completed a Type B meeting with the FDA and received guidance on the registrational path to advance INB-100 for the treatment of AML.

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Every AML patient treated with INB-100 remains in complete remission (CR), and patients across both trials have exceeded expected progression-free survival (PFS) to date. These data continue to demonstrate the broad clinical potential of gamma-delta T cells for difficult-to-treat cancers and provides support for the advancement of these therapies into Phase 2 trials.

As of August 1, 2024, no new relapses have been reported since the clinical updates provided at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the European Hematology Association (EHA) (Free EHA Whitepaper) annual meetings.

"Our gamma-delta T cell therapies, engineered with our industry-leading manufacturing technology, continue to demonstrate their potential to eliminate residual cancer cells and to revolutionize cancer treatment," said William Ho, CEO and co-founder of IN8bio. "The safety profile of gamma-delta T cells has been manageable and well-tolerated across both indications with no significant cell therapy-related toxicities reported to date in any patients across these Phase 1 trials."

Program Details as of August 1, 2024:

INB-100 for AML

FDA Guidance on Registrational Program: Following a Type B meeting with the FDA earlier this summer, IN8bio received regulatory guidance on advancing INB-100 for the treatment of AML as a post-transplant maintenance therapy, with relapse-free survival as the primary endpoint. To date, 100% of AML patients treated with INB-100 are in long-term CR, providing a promising path for the registrational trial. IN8bio plans to submit an Investigational New Drug (IND) application to the FDA in Q1 2025. Pending clearance, the Company could initiate a registrational trial for AML in 2025.
100% 1-year Relapse-Free Survival: All patients dosed in the Phase 1 investigator-sponsored trial continue to demonstrate relapse-free survival beyond one year. These patients are mostly classified as high-risk, a category where ~25% would typically be expected to relapse within 100 days post-transplant and up to 50% by one year.
AML Patient Outcomes: 100% of AML patients remain relapse-free after receiving their dose of INB-100. There have been no new relapses reported since the last update with a data cut-off on May 15, 2024. The previously reported patients with other leukemic diagnoses (ALL and MDS/MPN overlap with concurrent TP53 mutations) who relapsed are still alive. The proposed Phase 2 registrational trial will only include patients with AML, a highly aggressive leukemia with high relapse rates, where Phase 1 results to date have shown the most promising long-term responses.
Expansion Cohort: Enrollment in expansion cohort is ongoing, and all treated patients remain in CR, with several having been evaluated for at least 90 days post-transplant and the longest nearing seven months. Full enrollment of the 10-patient expansion cohort is expected by the end of 2024, with long-term follow up results anticipated in 2025.
Gamma-Delta T Cell Persistence: A significant increase in dose-dependent long-term expansion and persistence of circulating gamma-delta T cells continues to be observed up to day 365 post-infusion. This marks the first instance of an allogeneic cellular therapy demonstrating both persistence and expansion over this extended time frame. Cell persistence potentially allows for the gamma-delta T cells to conduct longer immune surveillance to prevent relapse.
INB-200 for GBM

Novel Cellular Therapy Approach: IN8bio’s proprietary drug-resistant immunotherapy (DRI) technology combines standard-of-care chemotherapy with gene-edited, chemotherapy-resistant gamma-delta T cells. Initial data points to a potential dose response across the three cohorts with dose-escalation ranging from a single dose in cohort 1, three doses in cohort 2, and up to six repeat doses in cohort 3. All patients in cohort 1 eventually relapsed. There have been no new relapses with a range of remission from 9.5 to 37.9 months in cohorts 2 and 3 to date. Multiple patients in these higher repeat dose cohorts have now exceeded the overall survival expected with standard-of-care alone relative to historical data.

MGMT-unmethylated GBM patients: Several patients in this group, who are typically poor responders and generally unresponsive to chemotherapy, have remained in remission longer than expected. Notably, one patient who received six doses of INB-200 has been in remission for over a year. Updated clinical data from this trial is expected to be presented in Q4 2024.

INB-400 in Phase 2 trial: This study is investigating six doses of autologous gamma-delta T cells in front-line GBM treatment in combination with standard-of-care. The trial is actively enrolling and treating patients at multiple leading cancer centers across the United States.
Mr. Ho, also commented, "These therapies take advantage of the gamma-delta T cells’ natural ability to target the heterogeneity of cancers, prevent immune escape and disease relapse. Multiple patients have now remained in progression-free remissions longer than expected with many now exceeding expected overall survival, based on historical data. The safety profile and long-term remissions observed with both INB-100 and INB-200, now exceeding three years, across two difficult indications, suggest a significant potential advancement for cellular therapies for cancer. With these compelling results to date, IN8bio stands at the forefront of innovation in oncology and gamma-delta T cell development."

Conference Call Details

IN8bio will host a conference call and webcast today, Monday, August 12, 2024, at 8:30 am ET. The webcast can be accessed by clicking this link and can also be accessed on the Events & Presentations page of the Company’s website. To participate in the live call, please register using this link. It is recommended that participants register at least 15 minutes in advance of the call. Once registered, participants will be informed of the dial-in number and will be provided a unique PIN.