On July 21, 2023 Imugene Limited (ASX:IMU), a clinical-stage immuno‐ oncology company, reported its Quarterly Cash Flow report (Appendix 4C) for the quarter ended 30 June 2023 (Presentation, Imugene, JUL 21, 2023, https://mcusercontent.com/e38c43331936a9627acb6427c/files/7feca463-a7dc-a00f-8897-cedeb2e36ecc/Quarterly_ActivitiesAppendix_4C_Cash_Flow_Report.pdf [SID1234633340]).

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On July 21, 2023 Genmab A/S (Nasdaq: GMAB) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the granting of conditional marketing authorization of epcoritamab (TEPKINLY) as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy (Press release, Genmab, JUL 21, 2023, View Source [SID1234633339]). The final European Commission decision on the indication for epcoritamab is anticipated later this year.

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"Today’s CHMP opinion is an important step forward in our mission to bringing innovative, readily available medicines like epcoritamab to patients in Europe who are in need of alternative treatment options for relapsed or refractory diffuse large B-cell lymphoma," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. "We look forward to continuing our work with AbbVie to develop epcoritamab as a potential core therapy across B-cell malignancies."

AbbVie’s application for the approval of epcoritamab is supported by results from the pivotal EPCORE NHL-1 phase 1/2 open-label, multi-center trial evaluating the safety and preliminary efficacy of epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell NHL, including DLBCL. The primary endpoint of the study was overall response rate, as assessed by an independent review committee (63.1 percent). The most common treatment-emergent adverse event was cytokine release syndrome.i Updated results were recently presented at multiple medical congresses.

"Diffuse large B-cell lymphoma is an aggressive and often treatment-resistant disease with limited therapeutic options for patients whose disease is refractory or who have experienced relapse after multiple lines of therapy," said Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department, Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris. "Subcutaneous epcoritamab could become a promising treatment option for the DLBCL community, and I look forward to the European Commission’s final decision."

DLBCL is an aggressive type of cancer that develops in the lymphatic system. It is the most common type of B-cell NHL worldwide and accounts for approximately 30 percent of all global cases. Because NHL affects B-cell lymphocytes, the disease and its subtypes, including DLBCL, are classified as B-cell malignancies.ii

Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization.

About the EPCORE NHL-1 Trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that includes a phase 1 first-in-human, dose escalation part; a phase 2a expansion part; and a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell NHL, including large B-cell lymphoma (LBCL) and DLBCL.iii Data from the dose escalation part of the study, which determined the recommended phase 2 dose, were published in September 2021.iv In the phase 2 expansion part, additional patients were treated with epcoritamab to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-cell NHLs who had limited therapeutic options.iii

The primary endpoint of the phase 2 expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, progression-free survival, overall survival, time to response, time to next therapy, and rate of minimal residual disease negativity. The most common treatment-emergent adverse events were cytokine release syndrome (49.7 percent; grade 1 or 2: 47.1 percent; grade 3: 2.5 percent), pyrexia (23.6 percent) and fatigue (22.9 percent). Results from the phase 2 expansion part of the study were published in December 2022.i More information can be found on www.clinicaltrials.gov.

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T-cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T-cells and CD20 on B-cells and induces T-cell mediated killing of CD20+ cells.v CD20 is expressed on B-cells and is a clinically validated therapeutic target in many B-cell malignancies, including DLBCL, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.vi,vii

The safety and efficacy of epcoritamab remain under evaluation in the European Union. Epcoritamab-bysp (EPKINLYTM) was recently approved in the United States and is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Epcoritamab is not approved in the European Union. If approved, epcoritamab will be marketed under the brand name TEPKINLY in all EU member states plus Liechtenstein, Norway and Iceland. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets throughout the year.

EPKINLY (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine Release Syndrome (CRS). CRS is common during treatment with EPKINLY and can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop symptoms of CRS, including fever of 100.4°F (38°C) or higher, dizziness or lightheadedness, trouble breathing, chills, fast heartbeat, feeling anxious, headache, confusion, shaking (tremors), or problems with balance and movement, such as trouble walking.

Due to the risk of CRS, you will receive EPKINLY on a "step-up" dosing schedule. The step-up dosing schedule is when you receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of your first cycle of treatment (cycle 1). You will receive your first full dose of EPKINLY on day 15 of cycle 1. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule. Before each dose in cycle 1, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of CRS with future cycles.

Neurologic problems. EPKINLY can cause serious neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY. Your healthcare provider may refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any symptoms of neurologic problems, including trouble speaking or writing, confusion and disorientation, drowsiness, tiredness or lack of energy, muscle weakness, shaking (tremors), seizures, or memory loss.
Due to the risk of CRS and neurologic problems, you should be hospitalized for 24 hours after receiving your first full dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will monitor you for symptoms of CRS and neurologic problems during treatment with EPKINLY, as well as other side effects, and treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with EPKINLY if you develop CRS, neurologic problems, or any other side effects that are severe.

Do not drive or use heavy or potentially dangerous machinery if you develop dizziness, confusion, tremors, drowsiness, or any other symptoms that impair consciousness until your symptoms go away. These may be symptoms of CRS or neurologic problems.

EPKINLY can also cause other serious side effects, including:

Infections. EPKINLY can cause serious infections that may lead to death. Your healthcare provider will check you for symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts. Low blood cell counts are common during treatment with EPKINLY and can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cell counts (neutropenia), which can increase your risk for infection; low red blood cell counts (anemia), which can cause tiredness and shortness of breath; and low platelet counts (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all of your medical conditions, including if you:

have an infection.
are pregnant or plan to become pregnant. EPKINLY may harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with EPKINLY. You should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY.
are breastfeeding or plan to breastfeed. It is not known if EPKINLY passes into your breast milk. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.
Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea.

These are not all the possible side effects of EPKINLY. Call your doctor for medical advice about side effects.

You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see the Full Prescribing Information and Medication Guide, including Important Warnings.

On July 21, 2023 Starpharma (ASX: SPL, OTCQX: SPHRY) reported that DEP HER2-zirconium, its HER2-targeted radiodiagnostic candidate, has demonstrated a favourable biodistribution profile, with excellent imaging contrast between tumour and normal tissues, as well as rapid uptake and high levels of tumour accumulation in a HER+ breast cancer model (Press release, Starpharma, JUL 21, 2023, View Source;mc_eid=bf52dd3418 [SID1234633338]). These are important features for a radiodiagnostic product for accurate diagnosis and monitoring of tumour lesions using PET-CT imaging. The study details and results are reported below.

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Starpharma’s DEP HER2-zirconium is a radiodiagnostic product that belongs to the rapidly growing "radiotheranostic" category – which includes both radiodiagnostic and radiotherapeutic products. DEP HER2-zirconium is designed to specifically diagnose, stage, and monitor HER2+ cancers with greater sensitivity, meaning that patients suffering from these cancers could be diagnosed earlier, more accurately, and monitored more closely during cancer treatment.

The study results are very encouraging as they confirm the optimised binding properties of DEP HER2-zirconium for targeted delivery and preferential uptake by cancer cells, and support a precision medicine approach for cancer patients. The combined effect of the novel pharmacological properties of DEP HER2-zirconium gives it an advantage in the promotion of selective tumour cell entry and support its targeted delivery mechanism to tumour cells, leaving normal cells relatively untouched.

Commenting on the significance of these findings, Clinical Pharmacology and Oncology specialist, Dr Paul Wabnitz, (MD, FRACP)3, said:

"Translated clinically, this technology has the potential to detect cancer cells at very low levels and better guide therapeutic decisions at earlier stages and at levels that were previously undetectable by current radiological methods. This has several advantages, including dose optimisation and better identifying the minimal dose level for an efficacious response, thereby minimising toxicity and promoting the quality of life and care of cancer patients undergoing therapy."

Dr Jackie Fairley, CEO of Starpharma, commented:

"Radiotheranostics and HER2 therapeutics are both rapidly growing categories with a number of highly successful product launches in recent years. The application of Starpharma’s DEP technology in the radiotheranostic area presents a substantial opportunity to expand the commercial opportunity for DEP. The DEP platform offers greater flexibility which allows a wide range of radioisotopes to be utilised."

HER2 and radiotheranostics market

The global radiotheranostics market was US$1.8 billion in 2022 and is expected to grow by over 10% annually to US$4.2 billion by 2030. There are already several successful marketed radiodiagnostics, such as Pylarify and Illuccix, which detect prostate cancer through PET-CT scans, with others in development.

HER2-based antibody products had total sales of ~US$11 billion in 2022, which included Herceptin (or trastuzumab), marketed by Roche/Genentech and the highly successful AstraZeneca product, Enhertu.

DEP HER2-zirconium study details and results

DEP HER2-zirconium utilises a novel single-domain antibody (sdAb), or nanobody, which is smaller than a full mAb, to target and bind to HER2+ tumour cells. The study assessed the biodistribution and imaging (diagnostic) performance of DEP HER2-zirconium compared with a HER2-targeted full antibody (trastuzumab/Herceptin), labelled with zirconium-89. Zirconium-89 is a radioisotope used for PET-CT imaging in cancer patients.

A HER2+ human breast cancer cell line (BT474) was grown as a tumour subcutaneously in mice. Biodistribution was measured by in vivo PET-CT imaging and quantitative ex vivo gamma counting at time points ranging from 4 hours to 120 hours after dosing with either DEP HER2-zirconium or trastuzumab-zirconium, with a target radioactivity of 3 MBq (megabecquerel) per dose.

In this study, DEP HER2-zirconium:

Showed significant accumulation in tumour (>25% of the injected dose per gram [ID/g] of tumour);
Was cleared more rapidly from the blood, and highly perfused organs such as heart and lung, than HER2 mAb trastuzumab-zirconium (see Figure 1);
Demonstrated a significantly higher tumour-to-blood ratio than trastuzumab-zirconium; and
Resulted in high tumour-to-organ ratios, delivering excellent specificity in imaging the HER2+ breast cancer model (see Figure 2).
Figure 1. Injected dose in blood over time, demonstrating more rapid clearance of DEP HER2-zirconium versus trastuzumab-zirconium.

In summary, the data reported here for DEP HER2-zirconium highlight its promise in radiotheranostics, due to its efficiency of tumour delivery and favourable PK and biodistribution characteristics. The study results demonstrate positive characteristics that are relevant to both radiodiagnostic and radiotherapeutic DEP-based products.

On July 20, 2023 EpiBiologics, a biotechnology company advancing a next-generation antibody-based protein degradation platform and pipeline for membrane and extracellular drug targets, reported that Ann Lee-Karlon, Ph.D., will join as Chief Executive Officer, President, and member of the Board of Directors (Press release, EpiBiologics, JUL 20, 2023, View Source [SID1234643976]). Dr. Lee-Karlon will focus on expanding EpiBiologics’ proprietary EpiTAC platform, establishing value-driven collaborations, and building the company’s pipeline of bispecific antibody protein degrader therapeutics.

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"I had the pleasure of working with Ann at Genentech and am confident her deep experience building therapeutic pipelines and leading strategic collaborations will be invaluable as EpiBiologics progresses novel protein degrader therapeutics toward the clinic," said David Schenkein, MD, general partner at GV. "We would like to thank Rami Hannoush for his leadership as co-founder and interim CEO and look forward to an exciting next stage of growth for EpiBiologics under Ann’s leadership."

Prior to EpiBiologics, Dr. Lee-Karlon served as Chief Operating Officer of Altos Labs. She joined Altos at its initiation in 2021 and was instrumental in building the foundation for rapid growth to 500 employees across three global sites. Before Altos, Dr. Lee-Karlon spent over 18 years at Genentech, most recently as Senior Vice President. During her tenure at Genentech, she led portfolio strategy and operations and had project leadership oversight for over 80 drug development teams from research and development through FDA approval and global launch. She led major corporate partnerships and programs, including Ocrevus for multiple sclerosis and Rituxan in immunology. Dr. Lee-Karlon holds a B.S. in bioengineering from UC Berkeley, an MBA from Stanford University, and a Ph.D. in bioengineering from UC San Diego, where she was a National Science Foundation Fellow.

"EpiBiologics has developed a groundbreaking platform to target membrane and extracellular proteins, leveraging a novel atlas of tissue-specific degrader antibodies," said Dr. Lee-Karlon, CEO of EpiBiologics. "Targeted extracellular protein degradation represents a new therapeutic modality with a wide range of applications including cancer, immunology, and neurological diseases. I’m excited to work with the outstanding scientific team, advisors, and leaders to deliver new and important treatment options for patients in need."

EpiBiologics also announced that the company brought the total series A round to $73 million with the addition of $23 million from new investors Digitalis Ventures, Taiho Ventures, and existing investor Codon Capital. In March, EpiBiologics launched with its $50 million series A financing with participation from Mubadala Capital, Polaris Partners, Vivo Capital, and GV.

EpiBiologics welcomes new members to its board of directors, including Samuel Bjork, partner at Digitalis Ventures, and Seiji Miyahara, Ph.D., senior investment director at Taiho Ventures. Board member Mitchell Mutz, Ph.D., of Vivo Capital, who led the company’s efforts to close the series A extension, will continue in his role as the CFO of EpiBiologics.

"EpiBiologics has made tremendous progress with its leading-edge EpiTAC platform, which will unravel the underlying intricacies of disease biology to build precision therapeutics," said Mr. Bjork. "We are excited to work closely with Ann as the new CEO and the entire EpiBiologics team to bring the next generation of medicines to patients."

"With Ann’s strong track record in the biopharma industry, we are thrilled to join EpiBiologics’ syndicate of investors," said Dr. Miyahara. "We look forward to helping EpiBiologics continue to develop its novel bispecific antibody platform towards important treatments for a broad range of diseases."

On July 20, 2023 ADC Therapeutics reported that it plans to discontinue the Phase 2 LOTIS-9 clinical trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) and rituximab (Lonca-R) in unfit or frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, ADC Therapeutics, JUL 20, 2023, View Source [SID1234634579]). Given the challenges of defining the addressable segment of the difficult-to-treat unfit or frail DLBCL patient population, including many patients with significant active underlying co-morbidities, the benefit-risk profile does not support continuation of the LOTIS-9 trial.

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Following a meeting yesterday, the U.S. Food and Drug Administration (FDA) placed a partial clinical hold on the trial for new patient enrollment but will allow patients already on therapy who are deriving clinical benefit to remain on therapy after being reconsented. Following treatment of any reconsenting patients, the Company will conduct the necessary steps to conclude the trial and does not plan to continue studying this regimen in the unfit or frail previously untreated DLBCL patient population.

About (loncastuximab tesirine-lpyl)

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at www.ZYNLONTA.com.