On August 5, 2024 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, reported that the Malaysian National Pharmaceutical Regulatory Agency has approved a New Drug Application (NDA) for XPOVIO (selinexor) for two indications: (1) In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma (MM) who have received at least one prior therapy; and (2) in combination with dexamethasone for the treatment of adult patients with MM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy (Press release, Antengene, AUG 5, 2024, View Source [SID1234645350]).

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With a novel mechanism of action, XPOVIO is the world’s first approved orally-available, selective XPO1 inhibitor, which has already been approved in eight markets in APAC. This successful approval for XPOVIO in Malaysia will introduce novel therapies to the clinical management of patients with MM in Malaysia, benefiting many patients and their families in the country. To date, XPOVIO has also been included in national health insurance or reimbursement schemes in the mainland of China, Australia, Singapore and South Korea.

The ASEAN region, with its steady economic growth and a population exceeding 600 million, has become a significant potential market for global biomedical development. The accelerating aging population in ASEAN has increased the overall disease burden on patients and local communities, leading to a growing demand for novel therapeutics. Antengene, in efforts to fulfill its commitment to enhancing the health and well-being of the ASEAN population, has submitted NDAs for XPOVIO in Thailand and Indonesia, with approvals expected in the second half of 2024. Looking ahead, the company aims to introduce more innovative medicines to the ASEAN market, bringing improved healthcare to more patients in the region.

While bringing XPOVIO to more APAC markets, Antengene is also striving to expand the indications of XPOVIO. Leveraging the drug’s novel mechanism of action, Antengene is currently developing multiple combination regimens of XPOVIO for the treatment of various indications including myelofibrosis (MF), T-cell non-Hodgkin’s lymphoma (T-NHL), and endometrial cancer.

About XPOVIO (selinexor)

XPOVIO is the world’s first approved orally-available, selective inhibitor of the nuclear export protein XPO1. It offers a novel mechanism of action, synergistic effects in combination regimens, fast onset of action, and durable responses.

By blocking the nuclear export protein XPO1, XPOVIO can promote the intranuclear accumulation and activation of tumor suppressor proteins and growth regulating proteins, and down-regulate the levels of multiple oncogenic proteins. XPOVIO delivers its antitumor effects through three mechanistic pathways: 1) exerting antitumor effects by inducing the intranuclear accumulation of tumor suppressor proteins; 2) reducing the level of oncogenic proteins in the cytoplasm by inducing the intranuclear accumulation of oncogenic mRNAs; 3) restoring hormone sensitivity by activating the glucocorticoid receptors (GR) pathway. To utilize its unique mechanism of actions, XPOVIO is being evaluated for use in multiple combination regimens in a range of indications. At present, Antengene is conducting multiple clinical studies of XPOVIO in the mainland of China for the treatment of relapsed/refractory hematologic malignancies and solid tumors (3 of these studies are being jointly conducted by Antengene and Karyopharm Therapeutics Inc. [Nasdaq:KPTI]).

On August 5, 2024 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), reported that a fourth patient enrolled in the Company’s Phase 2a clinical trial investigating narmafotinib in the treatment of advanced pancreatic cancer (the ACCENT trial) has recorded a confirmed partial response (Press release, Amplia Therapeutics, AUG 5, 2024, View Source [SID1234645349]).

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A total of 50 patients are planned for the Phase 2a ACCENT trial, recruited in two cohorts. In the first cohort of 26 patients, 6 or more patients with confirmed partial or complete responses are required to initiate recruitment of the second cohort of 24 patients. We have previously reported that three (3) confirmed partial responses have already been observed in the first patient cohort. This latest confirmed partial response means that only a further two (2) confirmed responses (partial or complete) are required for the trial’s interim analysis to support recruitment of the additional 24 patients in the second cohort of the trial.

The formal term ‘confirmed partial response’ means in these patients there is at least a 30% decrease in the overall size of tumour lesions, with no new tumour lesions, sustained over a two-month period, while a confirmed complete response refers to a total absence of tumour lesions over a two-month period.

Amplia CEO and MD Dr Chris Burns commented: "The activity of narmafotinib in the ACCENT trial continues to be very positive, consistent with our previous clinical and preclinical data. We remain on track to complete the interim analysis by the end of this quarter."

The Company will provide further updates on the trial as recruitment proceeds.

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.

About Narmafotinib

Narmafotinib (AMP945) is the company’s best-in-class inhibitor of the protein FAK, a protein overexpressed in pancreatic and other cancers, and a drug target gaining increasing attention for its role in solid tumours. The drug, which is a highly potent and selective inhibitor of FAK, has shown promising data in a range of preclinical cancer studies. The drug has successfully completed a healthy volunteer study, and is currently in an open-label Phase 2a trial in pancreatic cancer where a combination of narmafotinib and the chemotherapies gemcitabine and Abraxane is being assessed for safety, tolerability and efficacy.

About the ACCENT Trial

The ACCENT trial is entitled ‘A Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination with Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients’.

The ACCENT trial explores the use of narmafotinib in combination with standard-of-care chemotherapy of gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer. The trial is a single-arm open label study conducted in two stages. The firststage (Phase 1b), completed in November 2023, identified a 400 mg oral daily dose of narmafotinib, given in the days preceding regular chemotherapy infusion, as safe and well tolerated. This second stage (Phase 2a), of the trial is designed to assess drug efficacy in combination with gemcitabine and Abraxane. The primary endpoints are Objective Response Rate (ORR) and Duration on Trial (DOT) with secondary endpoints being Progression Free Survival (PFS) and Overall Survival (OS). Safety and tolerability will continue to be assessed.

More information about the ACCENT trial, including a list of participating sites, can be found via the Amplia Therapeutics website and at ClinicalTrials.gov under the identifier NCT05355298.

On August 5, 2024 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and other serious diseases, reported financial results for the second quarter ended June 30, 2024 and provided a review of recent business updates and internal clinical-stage programs (Press release, Xencor, AUG 5, 2024, View Source [SID1234645347]).

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"Xencor’s clinical focus is developing high-potential, first-in-class bispecific T-cell engagers and additional XmAb candidates that leverage our differentiated technology platforms. The expanding opportunities for engineered antibodies, T-cell engagers and other bispecifics have encouraged us to advance a range of new XmAb candidates, and we plan to announce our next candidates for clinical development in the coming months," said Bassil Dahiyat, Ph.D., president and chief executive officer of Xencor. "We remain enthusiastic by the progress of our clinical-stage T-cell engager programs and advancements within the platform to date in 2024. Our dose-escalation studies of XmAb819 (ENPP3 x CD3) in clear cell renal cell carcinoma and XmAb808 (B7-H3 x CD28) in advanced solid tumors remain on track to reach target dose levels by year end, and XmAb541 (CLDN6 x CD3) is off to a strong clinical start with initial study enrollment."

Bispecific Antibody Programs Advancing in Internal Clinical Development

XmAb819 (ENPP3 x CD3): XmAb819 is a bispecific T-cell engager in Phase 1 clinical development for patients with advanced clear cell renal cell carcinoma (ccRCC). XmAb819 is designed to engage the immune system, activating T cells for highly potent and targeted killing of tumor cells expressing ENPP3, an antigen highly expressed in ccRCC. Xencor’s XmAb 2+1 multivalent format used in XmAb819 enables greater selectivity of ENPP3-expressing tumor cells compared to normal cells, which express lower levels of ENPP3. Xencor is advancing through dose-escalation cohorts in an ongoing Phase 1 study, and the Company anticipates reaching target dose levels by year end.

XmAb808 (B7-H3 x CD28): XmAb808 is a tumor-selective, co-stimulatory bispecific T-cell engager in Phase 1 clinical development, in combination with pembrolizumab for patients with advanced solid tumors. XmAb808 binds to the broadly expressed tumor antigen B7-H3 and is constructed with the XmAb 2+1 format. Co-stimulation is required for T cells to achieve full activation, and targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells when the antibodies are bound to tumor cells. Xencor is advancing through dose-escalation cohorts in an ongoing Phase 1 study, and the Company anticipates reaching target dose levels by year end.

XmAb541 (CLDN6 x CD3): XmAb541 is a bispecific T-cell engager in Phase 1 clinical development for patients with advanced ovarian cancer and other solid tumor types. XmAb541 is designed to engage the immune system, activating T cells for highly potent and targeted killing of tumor cells expressing Claudin-6 (CLDN6), a tumor-associated antigen. Xencor’s XmAb 2+1 multivalent format used in XmAb541 enables greater selectivity for cells expressing CLDN6 over similarly structured Claudin family members, which may be expressed on normal tissue. The first patient was dosed in a Phase 1 dose-escalation study earlier this year.

Vudalimab (PD-1 x CTLA-4): Vudalimab, a selective dual checkpoint inhibitor of PD-1 and CTLA-4, is advancing in multiple clinical studies, including a monotherapy study in patients with clinically defined high-risk metastatic castration-resistant prostate cancer (mCRPC; Study XmAb717-05), a study in combination with docetaxel in patients with mCRPC (Study XmAb717-04), and a study in combination with chemotherapy in patients with non-small cell lung cancer (Study XmAb717-06). Xencor continues to anticipate a data update and decision whether to advance vudalimab for patients with mCRPC in the first half of 2025.
Recent Business Updates

Regained exclusive worldwide rights to plamotamab (CD20 x CD3), a Phase 2 ready, subcutaneously administered, immune-cell directed bispecific T-cell engager. Xencor advanced plamotamab through Phase 1 clinical development and is reviewing its potential for addressing unmet medical needs of patients.

Concluded Phase 1 studies of XmAb564 (IL2-Fc in autoimmune disease) and XmAb662 (IL12-Fc in solid tumors) in the first half of 2024, consistent with prior guidance.
Financial Guidance: Based on current operating plans, Xencor expects to end 2024 with between $475 million and $525 million in cash, cash equivalents and marketable debt securities, and to have cash to fund research and development programs and operations into 2027.

Financial Results for the Second Quarter and Six Months Ended June 30, 2024

Cash, cash equivalents and marketable debt securities totaled $585.0 million as of June 30, 2024, compared to $697.0 million as of December 31, 2023.

Revenues for the second quarter ended June 30, 2024 were $17.0 million, compared to $45.5 million for the same period in 2023. Revenues earned in the second quarter of 2024 were primarily non-cash royalty revenue from Alexion and MorphoSys/Incyte and licensing revenue from multiple licensees, compared to the same period in 2023, which were primarily research revenue from the second J&J collaboration, royalty revenue from Alexion and milestone revenue from Zenas. Revenues for the six months ended June 30, 2024 were $29.8 million, compared to $64.5 million for the same period in 2023. Revenue for the six-month period in 2024 were primarily non-cash royalty revenue from Alexion and MorphoSys/Incyte, compared to the same period in 2023, which were primarily research revenue from the second J&J collaboration, royalty revenue from Alexion and milestone revenue from J&J and Zenas.

Research and development (R&D) expenses for the second quarter ended June 30, 2024 were $61.5 million, compared to $60.1 million for the same period in 2023. R&D expenses for the six months ended June 30, 2024 were $118.4 million, compared to $125.6 million for the same period in 2023. Increased R&D spending for the second quarter of 2024 compared to 2023 and decreased R&D spending for the first six months of 2024 compared to 2023 are primarily due to increased spending on research and early-stage programs and decreased spending on XmAb104 (PD-1 x ICOS).

General and administrative (G&A) expenses for the second quarter ended June 30, 2024 were $17.7 million, compared to $11.5 million for the same period in 2023. G&A expenses for the six months ended June 30, 2024 were $31.5 million, compared to $25.6 million for the same period in 2023. Increased G&A spending for the second quarter and first six months of 2024 compared to 2023 is primarily due to increased spending on corporate activities, including stock-based compensation costs related to employees retiring in April 2024.

Other income (expense) for the second quarter ended June 30, 2024 was $(5.0) million, compared to $4.0 million for the same period in 2023. Other expense for the second quarter of 2024, compared to other income for the same period in 2023, is primarily due to unrealized and realized losses recognized from the change in fair value and the sale of equity investments. Other income (expense) for the six months ended June 30, 2024 was $(15.8) million, compared to $4.0 million for the same period in 2023. Other expense for the first six months of 2024, compared to other income for the same period in 2023, is primarily due to an impairment charge on an equity investment without a readily determinable fair value.

Non-cash, stock-based compensation expense for the six months ended June 30, 2024 was $28.6 million, compared to $26.2 million for the same period in 2023.

Net loss attributable to Xencor for the second quarter ended June 30, 2024 was $66.0 million, or $(1.07) on a fully diluted per share basis, compared to net loss of $22.0 million, or $(0.37) on a fully diluted per share basis, for the same period in 2023. For the six months ended June 30, 2024, net loss attributable to Xencor was $134.0 million, or $(2.18) on a fully diluted per share basis, compared to net loss of $82.7 million, or $(1.38) on a fully diluted per share basis, for the same period in 2023.

The total shares outstanding were 61,766,054 as of June 30, 2024, compared to 60,600,060 as of June 30, 2023.

On August 5, 2024 Salubris Biotherapeutics, Inc. (SalubrisBio), a clinical-stage biotechnology company dedicated to discovering and developing novel complex biologic therapeutics, reported it has received approval from the European Medicines Agency (EMA) to initiate a Phase 1 clinical trial of JK06 in a basket of solid tumors known to express 5T4 (Press release, Salubris Biotherapeutics, AUG 5, 2024, View Source [SID1234645345]).

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5T4 is an oncofetal protein that is overexpressed in a wide range of tumor types, including lung, breast, renal and genitourinary cancers, and is associated with a poor prognosis and more aggressive tumor progression. JK06 is a first-in-class quadrivalent, biparatopic antibody drug conjugate (ADC) that selectively targets 5T4 with an MMAE payload. JK06 has demonstrated picomolar affinity for 5T4 and rapid internalization due to the biparatopic design. Together with stable, site-specific payload conjugation, JK06 has further demonstrated robust efficacy and a clean safety profile in non-clinical studies.

"JK06 has shown an exceptional therapeutic window in non-clinical evaluation, and we believe it has the potential to be a first-in-class and differentiated therapy for patients with 5T4-associated cancers," said Sam Murphy, Chief Executive Officer of SalubrisBio. "We are thrilled to be advancing into the clinic following the EMA’s decision and explore JK06’s ability to improve outcomes for patients."

JK06 will be evaluated in an open-label, dose-escalation and expansion study to assess the safety, pharmacokinetics, and preliminary efficacy of JK06. Phase 1 recruitment is expected to commence in Q3 2024, with up to 155 subjects planned for enrollment.

"5T4 is a very promising tumor target, highly expressed on tumor cells from multiple cancer types as opposed to normal adult tissue and correlated with poor prognosis. 5T4 upregulation is playing a major role in the cancer heterogeneity, aggressiveness and metastatic potential, all of which are key factors that make these cancers harder to treat," said Dr Nuria Kotecki, from Jules Bordet Institute in Brussels. "JK06 holds significant therapeutic potential by enhancing binding affinity and specificity, allowing for more effective delivery of cytotoxic agents directly to 5T4 cells, and we look forward to further evaluating it’s utility in the Phase 1 clinical trial."

On August 5, 2024 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a late-stage biopharmaceutical company committed to developing novel, transformative therapies for serious rare diseases, reported that it received U.S. Food and Drug Administration (FDA) clearance for its Investigational New Drug (IND) application for RZ358 (ersodetug) to treat hypoglycemia in patients with tumor hyperinsulinism (HI) (Press release, Rezolute, AUG 5, 2024, View Source [SID1234645344]). The Company is initiating start-up activities for the study which will be primarily conducted in the U.S. and patient enrollment is planned to commence in the first half of 2025. Ersodetug is also being studied in an ongoing global, pivotal, Phase 3 clinical trial in patients with congenital HI. Topline data from that study is expected in mid-2025.

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"Hypoglycemia associated with tumor HI requires treatment to prevent serious adverse outcomes and to improve patients’ daily function and quality of life, including enabling them to receive tumor directed therapies," said Brian Roberts, M.D., Chief Medical Officer at Rezolute. "We are encouraged by the substantial real-world benefit we’ve witnessed in tumor HI patients who have previously received ersodetug in our Expanded Access Program, coupled with the safety and efficacy demonstrated in clinical studies in patients with congenital HI, a similar condition. We believe that the clearance of our IND for this Phase 3 study reflects FDA’s recognition of the potential for ersodetug to address this serious unmet need and we are excited to be moving one step closer to a potential universal treatment for hypoglycemia caused by all forms of HI."

The Phase 3 registrational study is a double-blind, randomized, placebo-controlled trial of 24 participants who have inadequately controlled hypoglycemia because of tumor HI. Eligible participants will be randomized in 1:1 fashion (12 per treatment arm) to receive ersodetug 9 mg/kg per week or matched placebo, as an add-on to standard of care. Up to 24 additional participants may be enrolled into an open-label arm, in participants whose hypoglycemia is being managed by IV glucose in a hospital setting. Following a 6-week pivotal treatment period, all participants may receive ersodetug in open-label extension. The primary endpoint is the change in Level 2 (moderate) and Level 3 (severe) hypoglycemia events by self-monitored blood glucose. Additional endpoints include overall hypoglycemia events, time in hypoglycemia by continuous glucose monitor, patient reported quality of life, hospitalizations, and change in glucose requirements (for open-label hospitalized participants).

Ersodetug is a fully human monoclonal antibody that binds to an allosteric site on the insulin receptor at target tissues such as liver, fat and muscle. Ersodetug counteracts excess insulin receptor activation caused by insulin and related hormones thereby correcting hypoglycemia. Ersodetug has the potential to be universally effective at treating hypoglycemia caused by any form of HI, including congenital or acquired forms.

About Tumor Hyperinsulinism (HI)

Tumor HI is a rare disease that may be caused by two distinct types of tumors: islet cell tumors (ICTs) and non-islet cell tumors (NICTs), both of which lead to hypoglycemia as a result of excessive activation of the insulin receptor. Insulinomas are the most common type of ICT and may cause hypoglycemia by stimulating the over production of insulin. A variety of different NICTs, particularly hepatocellular carcinoma, can cause hypoglycemia by producing and secreting insulin-like paraneoplastic substances such as IGF-2 that bind to and activate the insulin receptor. With high morbidity and mortality rates within tumor HI, there remains a significant unmet need for new therapies directed at hypoglycemia treatment. Ersodetug has shown real-world benefit in patients with insulinoma and preclinical studies have shown that ersodetug can similarly blunt IGF-2 and insulin-mediated insulin-receptor signaling.