On August 17, 2021 Aptevo Therapeutics Inc. ("Aptevo" or "the Company") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported the publication of a peer-reviewed research article in the prestigious oncology journal Cancers (Press release, Aptevo Therapeutics, AUG 17, 2021, View Source [SID1234586696]). The research article reports the results of a multi-institutional Phase 1 clinical study of Aptevo’s lead leukemia drug candidate APVO436 in 46 adult patients with relapsed or refractory AML or MDS.

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"AML and MDS are common forms of blood cancer in adults. Patients with AML or MDS who relapse following available standard of care treatments have a dismal prognosis and they are in urgent need for new treatment options," explained Dr. Fatih Uckun, a leukemia expert and Chief Clinical Advisor at Aptevo, who is the lead author of the new article. He added: "This study was undertaken to evaluate if AML or MDS patients who have failed the available standard treatment options could tolerate and potentially benefit from a new form of therapy which activates patient’s own immune system against AML cells. Specifically, APVO436 is a recombinant protein engineered to redirect host immune system to leukemic cells from patients with hematologic malignancies that express on their surface a protein known as the interleukin 3 receptor or CD123."

A total of 46 relapsed AML/MDS patients received APVO436 as weekly intravenous (IV) infusions at 10 different dose levels. APVO436 exhibited a favorable safety profile with acceptable tolerability and generally manageable drug-related adverse events (AEs), and its maximum tolerated dose (MTD) was not reached at a weekly dose of 60 mcg. The most common APVO436-related AEs were infusion-related reactions (IRR) occurring in 13 (28.3%) patients and cytokine release syndrome (CRS) occurring in 10 (21.7%) patients. The incidence of severe CRS was 8.7%.

Promising clinical activity was observed in 11 of 40 patients (27.5%) evaluable for efficacy: Eight of 34 (23.5%) evaluable relapsed AML patients showed favorable responses including prolonged stable disease (SD), >50% reduction of leukemic cell count in the bone marrow with clearance of leukemic cells from the blood, partial remissions (PR), and complete remissions (CR). Seven of these 8 with favorable responses had failed 2-4 prior lines of anti-AML therapy and one 76 years old patient had relapsed after achieving a remission on frontline venetoclax plus decitabine therapy. Furthermore, 3 of 6 (50%) evaluable relapsed MDS patients had a marrow CR.

The median survival was >300 days for the 8 relapsed AML patients with a favorable response. By contrast, the median survival for the remaining 31 AML patients was 100 days. Five of the 8 AML patients with favorable responses remained alive at 110, 124, 323, 352, and 395 days, respectively.

A clinically active, so-called "recommended phase 2 dose (RP2D) level" was identified for further clinical development of APVO436. Of 9 patients treated at the RP2D level, 4 (44.4%) showed evidence of clinical activity: 2 AML patients achieved a CR, one MDS patient achieved a marrow CR, and the disease was stabilized in an AML patient with a time to progression of more than 7 months.

"The safety profile and preliminary evidence of efficacy of APVO436 in relapsed AML and MDS patients warrant further investigation of its clinical potential." stated Dr. Uckun. "We are excited about the potential clinical impact of our lead leukemia drug candidate, and we are hopeful that the continued development of APVO436 may provide the foundation for a potentially more effective combination therapy as a new standard of care regimen that is less likely to fail." added Marvin White, CEO of Aptevo.

The article "A Clinical Phase 1B Study of the CD3xCD123 Bispecific Antibody APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome" has been published in Cancers as part of the Special Issue "Acute Myeloid Leukemia (AML)" and is available online:

Abstract: View Source
PDF Version: View Source/pdf
Special Issue:
View Source

Citation Reference: Uckun, F.M.; Lin, T.L.; Mims, A.S.; Patel, P.; Lee, C.; Shahidzadeh, A.; Shami, P.J.; Cull, E.; Cogle, C.R.; Watts, J. A Clinical Phase 1B Study of the CD3xCD123 Bispecific Anti-body APVO436 in Patients with Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. Cancers 2021, 13, 4113. View Source

About APVO436
Overexpression of CD123 is the hallmark of many forms of leukemia. Aptevo’s lead proprietary drug candidate, APVO436 is a bispecific ADAPTIR that targets CD123 x CD3 and is designed to redirect the immune system of the patient to destroy leukemia cells expressing the target CD123 molecule on their surface. This antibody-like recombinant protein therapeutic is designed to engage both leukemia cells and T-cells of the immune system and bring them closely together to trigger a rapid and complete destruction of leukemia cells. APVO436 has been engineered using Aptevo’s proprietary and enabling bioengineering methods and is designed to reduce the likelihood and severity of an unintended and potentially harmful activation of the immune system. APVO436 has been engineered to stay in the blood circulation long enough to locate, bind with and destroy target leukemia cells. APVO436 has received orphan drug designation ("orphan status") for AML according to the Orphan Drug Act.

On August 17, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160) and EUSA Pharma (UK), Ltd. reported that the China National Medical Products Administration (NMPA) has granted QARZIBA (dinutuximab beta) conditional approval for the treatment of high-risk neuroblastoma in patients aged 12 months and above who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with a history of relapsed or refractory (R/R) neuroblastoma with or without residual disease (Press release, BeiGene, AUG 17, 2021, View Source [SID1234586697]). Dinutuximab beta is a targeted immunotherapy approved by the European Medicines Agency (EMA).i

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"For these young patients fighting neuroblastoma in China, we are proud to bring the first approved treatment."

"Dinutuximab beta represents an important biologic therapy for pediatric patients in China, having been listed in the first batch of New Drugs in Urgent Clinical Need Marketed Overseas by the NMPA," commented Xiaobin Wu, Ph.D., President, Chief Operating Officer, and General Manager of China at BeiGene. "For these young patients fighting neuroblastoma in China, we are proud to bring the first approved treatment."

"We are delighted that the benefit of dinutuximab beta has been recognized in China. This approval represents an important milestone in our mission and collaboration with BeiGene of bringing innovative cancer and rare disease therapies to patients," said Carsten Thiel, Ph.D., Chief Executive Officer of EUSA Pharma.

The approval of dinutuximab beta in China for the treatment of patients with high-risk neuroblastoma was supported by clinical results available from key trials conducted by SIOPEN (The International Society of Paediatric Oncology Europe Neuroblastoma Group) in collaboration with APEIRON Biologics and EUSA Pharma. These randomized controlled trials evaluated the efficacy of dinutuximab beta by comparing the administration of dinutuximab beta with and without interleukin-2 (IL-2) in the first-line treatment of patients with high-risk neuroblastoma and in two single-arm studies in the R/R setting. In the SIOPEN trial (HR-NBL1), the five-year event-free survival (EFS) rate in patients treated with dinutuximab beta was 57% vs. 42% of historical controls (p<0.01) and the five-year overall survival (OS) rate was 64% vs. 50% (p≤0.0001).ii The safety of dinutuximab beta has been evaluated in 514 patients. The most common adverse reactions were pyrexia and pain that occurred despite analgesic treatment. Other frequent adverse reactions were hypersensitivity, vomiting, diarrhea, capillary leak syndrome, and hypotension.

About QARZIBA (dinutuximab beta)

QARZIBA is a monoclonal antibody that is specifically directed against the carbohydrate moiety of disialoganglioside 2 (GD2), which is overexpressed on neuroblastoma cells. Dinutuximab beta was approved by the European Commission in 2017 (See EMA Summary of Product Characteristics (SmPC)) and is indicated for the treatment of high-risk neuroblastoma in patients aged 12 months and above, who have previously received induction chemotherapy and achieved at least a partial response, followed by myeloablative therapy and stem cell transplantation, as well as patients with a history of relapsed or refractory neuroblastoma, with or without residual disease. Prior to the treatment of relapsed neuroblastoma, any actively progressing disease should be stabilized by other suitable measures.

On August 17, 2021 MorphoSys AG (FSE: MOR; NASDAQ: MOR) reported that Incyte, its development and commercialization partner for tafasitamab, entered into a collaboration and license agreement with a subsidiary of InnoCare for tafasitamab in Greater China (Press release, MorphoSys, AUG 17, 2021, View Source [SID1234586675]). Under the terms of the agreement, InnoCare will receive the rights to develop and exclusively commercialize tafasitamab, a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody, in hematology-oncology in mainland China, Hong Kong, Macau and Taiwan.

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In January 2020, MorphoSys and Incyte entered into a collaboration and license agreement to develop and commercialize MorphoSys’ proprietary anti-CD19 antibody tafasitamab globally. MorphoSys and Incyte co-commercialize tafasitamab in the U.S., and Incyte holds the development and commercialization rights for tafasitamab outside the U.S. MorphoSys will receive tiered royalties on ex-U.S. net sales.

About Tafasitamab
Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb(R) engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Monjuvi(R) (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Monjuvi(R) is being co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.

In June 2021, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending the conditional marketing authorization of tafasitamab in combination with lenalidomide, followed by tafasitamab monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT). The CHMP opinion is currently being reviewed by the European Commission, which has the authority to grant marketing authorization for medicinal products in the European Union (EU).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials.

Monjuvi(R) is a registered trademark of MorphoSys AG.
XmAb(R) is a registered trademark of Xencor, Inc.

On August 17, 2021 Istari Oncology, Inc., a clinical-stage biotechnology company focused on novel immunotherapy platforms for the treatment of solid tumors, reported the company is proceeding with the expansion of its LUMINOS-103 trial, with a new sub-study evaluating PVSRIPO in adult patients with head and neck squamous cell carcinoma (HNSCC) (Press release, Istari Oncology, AUG 17, 2021, View Source [SID1234586698]). LUMINOS-103 is a Phase I/II, open-label, multi-center, single-arm basket trial evaluating the administration of PVSRIPO with or without PD-1/L1 inhibitors across multiple tumor types. The company began the LUMINOS-103 basket trial earlier this year, opening recruitment to patients with bladder cancer in two separate cohorts.

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Istari Oncology’s PVSRIPO is a novel intratumoral viral immunotherapy that activates a patient’s innate and adaptive immune system to facilitate a systemic anti-tumor immune response. PVSRIPO enters solid tumor cells and antigen presenting cells (APCs) in the tumor microenvironment via CD155 (the poliovirus receptor). CD155 is expressed on nearly all solid tumors, giving PVSRIPO the potential to treat a variety of cancers.

"We enter this next phase of PVSRIPO development in patients with solid tumors with great enthusiasm as we progress toward further evaluating the impact of PVSRIPO on patients with head and neck squamous cell carcinoma," said Matt Stober, president and chief executive officer at Istari Oncology. "With patient recruitment underway for our LUMINOS-103 bladder cancer cohorts, and the expectation that future cohorts focusing on other solid tumors will be added in the near future, we are proud to broaden the PVSRIPO clinical development program."

HNSCC is a heterogeneous group of malignant tumors typically caused by alcohol and tobacco consumption, although an increasing number of HNSCC cases arise due to persistent infection with high-risk human papilloma virus (HPV). The treatment of HNSCC remains challenging, and a substantial proportion of patients with this condition die from their disease, especially those with recurrent and metastatic disease.1

"This year more than 66,000 people in the U.S. – approximately 49,000 men and 18,000 women – will develop head and neck cancer," said Amanda Hollinger, MPA, executive director, Head & Neck Cancer Alliance. "As we continue to focus on advancing prevention, detection, treatment, and rehabilitation of people with head and neck cancer, we will be closely watching the progress of Istari’s head and neck sub-study with great anticipation and optimism."

For more information about Istari Oncology and its ongoing clinical trials and research on PVSRIPO, visit www.istarioncology.com.

About PVSRIPO

PVSRIPO is an investigational immunotherapy based on the live attenuated Sabin type 1 polio vaccine that has been genetically modified for safety. PVSRIPO has a distinct target (the poliovirus receptor CD155), which is widely expressed in neoplastic cells of most solid tumors. Via CD155, PVSRIPO targets tumors with three key mechanisms: 1) engagement and activation of antigen presenting cells (APCs), leading to T cell priming and sustained, systemic anticancer immunity; 2) direct tumor cell killing and antigen release; and 3) amplification of the immune response via recall of polio vaccine-specific T cells. PVSRIPO has been granted Breakthrough Therapy and Orphan Drug Designation status by the U.S. Food and Drug Administration in recurrent glioblastoma, and Fast Track and Orphan Drug Designation status in refractory melanoma.

On August 17, 2021 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells within the patient’s body, reported a business and clinical progress update for the second quarter 2021 (Press release, Cue Biopharma, AUG 17, 2021, View Source [SID1234608273]).

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"During the second quarter 2021, we continued to make significant clinical progress advancing our IL-2 based CUE-100 series, represented by the Phase 1a/1b monotherapy trial of CUE-101 and combination-therapy trial with KEYTRUDA (pembrolizumab). In addition, we have continued with the development and expansion of our pipeline programs and technology platforms, and also enhanced our capital resources," said Daniel Passeri, chief executive officer of Cue Biopharma. "Importantly, we recently reported a confirmed partial response (PR) in a patient from our ongoing Phase 1 monotherapy dose escalation trial of CUE-101 and look forward to providing further details on this patient response during the quarterly update call. Our Phase 1 monotherapy dose escalation and expansion study is now in dose expansion and our combination study with pembrolizumab continues in dose escalation. During the call, we will also highlight the development implications for CUE-101 and potential of the CUE-100 series and Immuno-STAT platform."

Kerri-Ann Millar, chief financial officer of Cue Biopharma, added, "We continue to be in a solid financial position and deployed our at-the-market (ATM) common stock facility during the second quarter to extend the anticipated operational runway further into the fourth quarter of 2022."

Recent News & Business Updates

Reported first patient dosed in the Part B expansion of its CUE-101 Phase 1 monotherapy clinical trial in HPV+ second line and beyond head and neck squamous cell carcinoma (HNSCC), at the recommended Phase 2 dose of 4mg/kg.
Presented preclinical data on CUE-401, the Company’s first autoimmune drug product candidate from the CUE-400 series, at the 2021 Federation of Clinical Immunology Societies (FOCIS) Annual Meeting.
Second Quarter 2021 Financial Results
The Company reported collaboration revenue of approximately $2.7 million and $1.1 million for the three months ended June 30, 2021 and 2020, respectively. The increase in collaboration revenue of $1.6 million was primarily due to additional research and development and contract manufacturing activities in preparation of an investigational new drug (IND) filing for its second drug product candidate from the IL-2 based CUE-100 series, CUE-102, planned for the first half of 2022.

Research and development expenses were $8.8 million and $8.1 million for the three months ended June 30, 2021 and 2020, respectively. The increase in research and development expenses of $0.7 million was primarily due to an increase in laboratory and drug substance manufacturing costs and clinical expenses.

General and administrative expenses were $4.3 million and $3.9 million for the three months ended June 30, 2021 and 2020, respectively. The increase in general and administrative expense of $0.4 million was primarily due to an increase in stock-based compensation expense and legal fees incurred in the second quarter of 2021 as compared to the same period in 2020.