ALT-P7 / Alteogen, 3SBio - LARVOL DELTA

Alteogen, Subcutaneous Injection ADC Patent Application… “Safe and Better Therapeutic Effect” [Google translation] (News1 Korea) - "Alteogen...announced on the 2nd that it has filed a domestic priority application for a subcutaneous injection (SC) formulation of an antibody drug conjugate (ADC)...Alteogen has been focusing on the possibility of developing a SC formulation ADC by incorporating its platform technology, ‘ALT-B4’, to overcome the limitations of existing ADC treatments....'This patent can strengthen the competitiveness of our own pipeline, 'ALT-P7,' which targets the HER2 receptor.'"

Patent • Breast Cancer • Oncology • Solid Tumor

From seaside to bedside: Current evidence and future perspectives in the treatment of breast cancer using marine compounds. (PubMed, Front Pharmacol) - "The main marine-derived drugs that have been studied for the treatment of BC are tubulin-binding agents (eribulin and plocabulin), DNA-targeting agents (cytarabine and minor groove binders-trabectedin and lurbinectedin) and Antibody-Drug Conjugates (ADCs)...Among these, clinical data are available on ladiratuzumab vedotin and glembatumumab vedotin in TNBC, and on disitamab vedotin and ALT-P7 in HER2-positive patients. A deeper knowledge of the mechanism of action and of the potential predictive factors for response to marine-derived drugs is important for their rational and effective use, alone or in combination. In this narrative review, we discuss the role of marine-derived drugs for the treatment of BC, although most of them are not approved, and the opportunities that could arise from the potential treasure trove of the sea for novel BC therapeutics."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • HER-2

Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers. (PubMed, Front Mol Biosci) - "A third HER2-directed ADC, disitamab vedotin (RC48), has been approved for locally advanced or metastatic gastric or gastroesophageal junction cancer by the NMPA (National Medical Products Administration) of China in 2021. In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges."

Journal • Review • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • ERBB4 • HER-2

Clinical Study of ALT-P7 to Determine Safety, Tolerability and Pharmacokinetics in Breast Cancer Patients (clinicaltrials.gov) - P1; N=27; Completed; Sponsor: Alteogen, Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

[VIRTUAL] First-in-human phase I study of ALT-P7, a HER2-targeting antibody-drug conjugate in patients with HER2-positive advanced breast cancer. (ASCO 2020) - P1 | "Background: ALT-P7 is an antibody-drug conjugate, in which two molecules of monomethyl auristatin E (MMAE) are site-specifically conjugated to a cysteine-containing peptide motif of trastuzumab variant. ALT-P7 was well tolerated to a dose of 4.2mg/kg in heavily pretreated HER2-positive advanced breast cancer. DLTs were observed at 4.8mg/kg, and 4.5mg/kg is under evaluation. The observed clinical activity warrants further evaluation in a phase 2 trial."

Clinical • P1 data • Alopecia • Breast Cancer • Cardiovascular • Dermatology • Dermatopathology • Fatigue • Gene Therapies • Heart Failure • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Pain • Pruritus • Solid Tumor • Thrombocytopenia • HER-2

Alteogen to diversify indications of ADC candidate in phase 2 trial (Korea Biomedical Review) - P1, N=30; NCT03281824; Sponsor: Alteogen; "Alteogen released the phase 1 clinical trial results of antibody-drug conjugate (ADC) to treat breast cancer. As the company confirmed the safety and efficacy of the drug candidate in the phase 1 study, it will diversify indications in the phase 2 study and seek an opportunity to license it out...Alteogen said the phase 1 results proved ALT-P7’s safety and efficacy. In addition, the phase 1 data showed that the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) were set at 4.5 mg/kg, the company said...The company said the disease control rate (DCR), which combines complete response (CR), partial response (PR), and stable disease (SD), was 72 percent (18 out of 25)."

Licensing / partnership • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology

Clinical Study of ALT-P7 to Determine Safety, Tolerability and Pharmacokinetics in Breast Cancer Patients (clinicaltrials.gov) - P1; N=30; Active, not recruiting; Sponsor: Alteogen, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Oct 2020 ➔ Jun 2021; Trial primary completion date: Jun 2020 ➔ Mar 2020

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

[ASCO 2020] Alteogen confirms safety, efficacy of HER2 breast cancer therapy (Korea Biomedical Review) - P1, N=30; NCT03281824; Sponsor: Alteogen; "The study results were released at the online poster session of the American Society of Clinical Oncology (ASCO) 2020...The disease control rate (DCR) of ALT-P7 was 72 percent, and the median progression-free survival (PFS) at a dose from 2.4 to 4.8 milligrams per kilogram was 6.2 months. The study showed dose-dependent pharmacokinetics of ALT-P7...Alteogen plans to evaluate further the efficacy of ALT-P7 in phase 2 and also will assess applicability for other various solid carcinomas, including gastric, urothelial, or biliary tract cancers..."

New P2 trial • P1 data • Biliary Cancer • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Urothelial Cancer

Alteogen presents the first-in-human data on ALT-P7, a HER2-targeting antibody-drug conjugate (ADC) at ASCO 2020 (Businesswire) - P1, N=30; NCT03281824; Sponsor: Alteogen, Inc; "In this trial, a total of 27 patients received study drug. The most common grade 3/4 adverse event (AE) was neutropenia. Other common treatment-related AEs of any grade were myalgia, fatigue, sensory neuropathy, alopecia, pruritus, and neutropenia. The dose limit toxicities (DLTs) were observed at 4.8 mg/kg with a single case of febrile neutropenia, hyperbilirubinemia, myalgia, and hyponatremia. The disease control rate (DCR) of ALT-P7 was 72%, and the median progression-free survival (PFS) was 6.2 months (95% CI: 2.5-9.9 months)."

P1 data • Breast Cancer • HER2 Breast Cancer • Oncology

Newly added product (clinicaltrials.gov) - P1, Breast Cancer, Gastric Cancer

Pipeline update • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Alteogen ends p-1 clinical trial of breast cancer treatment (Korea Biomedical Review) - "Alteogen said Tuesday that it has completed the phase 1 clinical trials of antibody-drug conjugate (ADC) ALT-P7, which became the first biobetter for breast cancer to pass the stage in Korea. The clinical trials of ALT-P7 by Alteogen, a biobetter developer, were conducted at Samsung Medical Center and Gacheon University Gil Medical Center, targeting progressive or recurrent positive human epidermal growth factor receptor 2 (HER2) patients...'ALT-P7 will enter phase 2 trial in the second half of this year to evaluate its efficacy in the dose as recommended by phase 1 trials. We are conducting negotiations with global partners for licensing it out'..."

Licensing / partnership • New P2 trial • Trial completion

Clinical Study of ALT-P7 to Determine Safety, Tolerability and Pharmacokinetics in Breast Cancer Patients (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Alteogen, Inc.; Enrolling by invitation ➔ Recruiting; Trial completion date: Mar 2019 ➔ Oct 2020; Trial primary completion date: Dec 2018 ➔ Jun 2020

Clinical • Enrollment status • Trial completion date • Trial primary completion date

HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in Breast Cancer. (PubMed, Int J Mol Sci) - "Currently, several HER2 directed antibody-drug conjugates are under clinical investigation for HER2 amplified but also HER2 expressing but not amplified breast tumors. In this article, we review the current preclinical and clinical evidence of the investigational drugs A166, ALT-P7, ARX788, DHES0815A, DS-8201a, RC48, SYD985, MEDI4276 and XMT-1522."

Journal • Review

Caveolin-1 is a potential complementary biomarker to select patients for HER2-targeted therapy with trastuzumab (IGCC 2019) - "However, clinical trials have failed to show efficacy with single HER2-targeted therapies (lapatanib, a reversible EGFR/HER2 kinase inhibitor or T-DM1, a trastuzumab drug conjugate) or dual antibody approaches (trastuzumab plus pertuzumab). Retrospective clinical and preclinical studies in PDXs demonstrated that the tumor uptake and therapeutic efficacy of trastuzumab patient-derived lower in HER2+/CAV1+when compared with HER2+/CAV1- gastric tumors. Conclusions Our studies demonstrate that while trastuzumab therapy has efficacy in patients with HER2-positive tumors containing low levels of CAV1, patients containing high levels of CAV1 might not benefit from this therapy."

Biomarker • Clinical