On May 16, 2022 Affimed N.V. (Nasdaq: AFMD) ("Affimed", or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported the presentation of new data on AFM24 and AFM28 in two posters at the 19th Meeting of the Society for Natural Immunity (NK2022) (Press release, Affimed, MAY 16, 2022, View Source [SID1234614667]).

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The AFM24 presentation showed correlative science data of the exposure and pharmacodynamic effects of the compound in patients with epidermal growth factor receptor (EGFR)-expressing solid tumors from the ongoing phase 1/2a study. The poster featured an analysis of the longitudinal effects of AFM24, a CD16A/EGFR‑targeting bispecific innate cell engager (ICE), in patients treated in the AFM24-101 phase 1/2a clinical study, confirming the mechanism of action of AFM24 on the innate immune system.

The correlative science data further supports the rationale for combining different therapeutic approaches in patients with EGFR-expressing solid tumors. AFM24 engages CD16A on natural killer (NK) cells and macrophages with higher affinity than monoclonal antibodies, and triggers antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), respectively, directed at EGFR-expressing cancer cells. Preclinical data have shown that AFM24 can induce NK cell-mediated killing of EGFR-positive solid tumor cell lines, independent of EGFR mutational status.

The analysis also showed activation of cytotoxic T cells in the periphery, and infiltration of T cells into the tumor bed, suggesting stimulation of anti-cancer immunity beyond the innate immune system and the possible engagement of the adaptive immune system. These data support the rationale for AFM24 as monotherapy and the two combinations that are currently under way in separate phase 1/2a studies – with autologous NK cell therapy and with immune checkpoint inhibition.

The AFM28 poster featured preclinical data on the anti-leukemic activity of the compound when pre-complexed and co-administered with allogeneic NK cells.

AFM28 is a novel ICE binding to CD16A on NK cells, and CD123 on acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) tumor cells. The novel bispecific engager binds with high affinity to NK cells stimulating them to destroy CD123-positive tumor cells via ADCC. In addition, AFM28 exhibits greater cell surface retention than conventional monoclonal antibodies, including Fc-enhanced IgG1.

Furthermore, the data presented at the conference demonstrate that AFM28 stimulates lysis of CD123-positive tumor cells in both formats, pre-complexed or when co-administered with NK cells. The poster also demonstrated the feasibility of cryopreserving AFM28 pre-complexed with NK cells whilst maintaining anti-tumor activity suggesting the promise for an off-the-shelf therapy targeting leukemic blasts and leukemic stem cells in patients with AML and MDS.

Poster details:
Title: Analysis of the Longitudinal Effects of AFM24, a CD16A/Epidermal Growth Factor Receptor Targeting (EGFR) Bispecific Innate Cell Engager, Confirms the Mechanism of Action and Supports the Rationale for Combination Approaches in Patients with EGFR-Expressing Solid Tumors
Authors: Gabriele Hintzen, Susanne Wingert, Michael Emig, Kerstin Pietzko, Uwe Reusch, Melissa M. Berrien‐Elliott, Todd A. Fehniger, Mark Foster, Paolo Nuciforo, Tyler Burns, Paulien Ravenstijn, Stefan Knackmuss, Bettina Rehbein, Joachim Koch, Arndt Schottelius, and Erich Rajkovic

Title: Novel Bispecific Innate Cell Engager AFM28 in Combination with Allogeneic NK Cells for the Treatment of CD123+ Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Jens Pahl, Jana-Julia Siegler, Armin Beez, Rebecca Hussong, Sabrina Purr, Lena Wagner, Nicole Schulze, Tatjana Kosbar, Uwe Reusch, Joachim Koch, Arndt Schottelius, Thorsten Ross, Christian Merz and Sheena Pinto

About AFM24
AFM24 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and EGFR, a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.
Affimed is evaluating AFM24 in patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies as monotherapy and in combinations with other cancer treatments. AFM24-101, a monotherapy, first-in-human phase 1/2a open-label, is a non-randomized, multi-center, multiple ascending dose escalation and expansion study. Additional details may be found at www.clinicaltrials.gov using the identifier NCT04259450. Furthermore, AFM24 is being evaluated in a phase 1/2a study in combination with Roche’s anti-PD-L1 checkpoint inhibitor atezolizumab (AFM24-102, NCT05109442). Affimed and NKGen Biotech have initiated a phase 1/2a study (AFM24-103), investigating AFM24 in combination with SNK01, NKGen Biotech’s NK cell product (NCT05099549).

About AFM28
AFM28 is a tetravalent, bispecific innate cell engager (ICE) that activates the innate immune system by binding to CD16A on innate immune cells and CD123-positive cells on myeloid malignancies. Developed on Affimed’s ROCK platform, it is designed to bring a new immunotherapeutic approach to patients with CD123-positive myeloid malignancies, including acute myeloid leukemia and myelodysplastic syndrome (MDS). AFM28 engages NK cells to initiate tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC), and binds CD123-positive cancer cells even at low expression levels. Clinical development is planned as both monotherapy and in combination with allogeneic NK cells in patients with relapsed/refractory CD123-positive leukemias.

On May 16, 2022 Ampio Pharmaceuticals, Inc. (NYSE American: AMPE), a biopharmaceutical company focused on the advancement of immunomodulatory therapies for the treatment of pain resulting from osteoarthritis in the knee and potentially other articular joints, reported financial results for the first quarter ended March 31, 2022 (Press release, Ampio, MAY 16, 2022, View Source [SID1234614683]).

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First Quarter Financial Results

Net Loss: Net loss was $5.6 million for the first quarter of 2022 compared to net loss of $3.7 million for the first quarter of 2021. Further details on these variances are below.
R&D Expenses: Research and development expenses were $3.7 million for the first quarter of 2022 compared to $2.3 million for the first quarter of 2021. The primary drivers of the increase were increases in (i) clinical trial and sponsored research expenses and (ii) salaries and professional fees.
G&A Expenses: General and administrative expenses were $3.3 million for the first quarter of 2022 compared to $1.5 million for the first quarter of 2021. The primary drivers of the increase were increases in (i) salaries and professional fees and (ii) non-cash stock-based compensation expense.
Cash Position / Liquidity: Cash and cash equivalents on March 31, 2022, totaled $28.8 million, compared to $33.9 million as of December 31, 2021. The decrease of $5.1 million is primarily attributable to cash required to fund business operations. Based on our current cash position and projection of operating expenses and capital expenditures, we believe that we will have sufficient liquidity to fund operations into the second half of 2023.

On May 16, 2022 Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biotechnology company focused on advanced therapies for autoimmune and inflammatory diseases, reported financial results for the full year ended December 31, 2021, as well as recent pipeline progress (Press release, Akari Therapeutics, MAY 16, 2022, View Source [SID1234614778]).

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"During the last twelve months, Akari has advanced nomacopan pre-clinical and clinical development programs, including three focus areas of autoimmune skin diseases, thrombotic microangiopathies, and progressive retinal diseases," said Rachelle Jacques, President and CEO of Akari Therapeutics. "Broad and deep research and development work is producing compelling science in diseases with complex pathologies and is providing the foundation for next steps in the development of bispecific recombinant nomacopan. Late-stage programs in pediatric HSCT-TMA and BP are active and advancing in Part A clinical studies, which will inform the pivotal Part B studies that will be the basis for potential regulatory submissions in the U.S. and Europe."

Full Year 2021 and Recent Clinical Highlights

Late-Stage Program Studying Investigational Nomacopan in Pediatric HSCT-TMA

Phase III Part A clinical trial sites are open and recruiting in the U.S. and Europe for investigation of nomacopan in pediatric HSCT-TMA.
Urgent unmet need exists in pediatric HSCT-TMA with no approved treatment options in the U.S. or Europe; currently the subset of patients Akari is studying are facing a mortality rate of ~80%
Nomacopan was granted Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration (FDA) for pediatric HSCT-TMA
Patient dosing is underway in the Part A study that has a recruitment goal of approximately seven patients, with a minimum of two patients in each of three age cohorts
Late-Stage Program Studying Investigational Nomacopan in Bullous Pemphigoid (BP)

FDA and European Medicines Agency (EMA) registration-directed Phase III Part A study of nomacopan in moderate and severe BP patients is open for enrollment following resolution of third-party supply chain partner issues that resulted in delays. Data from the Part A study will inform the pivotal Part B study that will be the basis for potential regulatory submissions in the U.S. and Europe
There are no approved therapies; superpotent topical steroid and high dose oral corticosteroid (OCS) are the current standards of care
The mortality rate in BP is approximately three-fold higher than the general population due to the disease itself, and infections and cardiovascular conditions that are more common in older patients and are exacerbated by treatment with high dose OCS.1
There is significant unmet need for an effective steroid-sparing therapy.
Nomacopan was granted Orphan Drug and Fast Track designations by the FDA and Orphan Drug designation from the EMA for the treatment of BP
Results from the completed Phase II study of subcutaneous nomacopan in patients with mild to moderate BP were published online in JAMA Dermatology in May 2022
The Phase II study advanced understanding of the nomacopan safety profile and informed duration of treatment in the ARREST-BP Phase III Part A clinical trial, which is currently open for enrollment
The multi-center, single arm nonrandomized controlled Phase II study included nine patients newly diagnosed or recurrent patients with mild to moderate active BP
Patients received subcutaneous nomacopan (30 mg once daily) with lesional mometasone from Day 1 to 21 of treatment and nomacopan only from Day 21 to Day 42
Seven of nine patients responded to nomacopan with three, regarded as complete responders, showing >80% reduction in BPDAI (BP disease activity index) activity and four patients showing >70% reduction in pruritis by Day 42; two of nine patients were non-responders
None of the nine patients reported Common Terminology Criteria for Adverse Events (CTCAE) grade three, four or five treatment-related adverse events
A poster outlining the design of the Phase III study of nomacopan in patients with moderate to severe BP was presented at the 2021 International Pemphigus & Pemphigoid Foundation (IPPF) Scientific Symposium
Pre-Clinical Program Studying Investigational Long-Acting PAS-Nomacopan for Geographic Atrophy/Dry Age-Related Macular Degeneration (GA/dAMD)

Akari has conducted pre-clinical studies that explore the importance of the leukotriene B4 (LTB4)-VEGF axis and the potential role of nomacopan’s bispecific inhibition of both C5 and LTB4 in treating GA/dAMD
Studies have indicated that while certain complement inhibitors slow the progression of GA, they may also promote choroidal neovascularization (CNV), which can harm the macula, damage vision,2,3 and require VEGF rescue therapy
LTB4 is a potent leukotactic agent that can increase retinal vascular endothelial growth factor (VEGF) a key driver of CNV. Inhibition of LTB4 may decrease the risk of CNV.4
Akari has conducted pre-clinical studies that explore the importance of the LTB4-VEGF axis and the potential role of nomacopan’s bispecific inhibition of both C5 and LTB4 in treating GA/dAMD
In a non-infectious allergic uveitis animal model, PAS-nomacopan reduced VEGF by more than 50% compared to saline control, equivalent to the inhibition caused by an anti-VEGF antibody. In addition, PAS-nomacopan was significantly more effective in reducing retinal inflammation than the anti-VEGF antibody.
A pre-clinical study presented at ARVO 2022 used an industry standard model of laser induced CNV. Intravitreal (IVT) PAS-nomacopan injected once during a 16-day treatment period was compared to an FDA-approved VEGF inhibitor for impact on neovascularization. The IVT single dose of PAS-nomacopan significantly reduced CNV (p=0.022) as compared to saline and was as effective as multiple IVT injections of the VEGF inhibitor (p=0.019.) Single IVT injection of PAS-nomacopan showed a trend towards reduced leakage on Day 14 (p = 0.097).
Currently approved therapies for retinal diseases injected directly into the vitreous cavity are typically administered monthly. Studies have shown that due to adverse effects (such as an increase in intraocular pressure [IOP]), discomfort and anxiety, IVT injection presents a heavy burden on patients
PASylation of nomacopan has the potential to make it long-lasting in the back of the eye and may provide a dosing interval that is more attractive to patients
Akari is continuing pharmacokinetic (PK) and pharmacodynamic (PD) work to optimize PAS-nomacopan with the aim of achieving safety and efficacy in GA, and meeting patient preferences for less frequent injections
Studies of Investigational Nomacopan in Inflammation-Implicated Lung Conditions

Advanced the study of investigational nomacopan in the treatment of inflammation-implicated lung conditions
The CORONET study evaluated compassionate use of investigational nomacopan in the treatment of hospitalized COVID-19 pneumonia patients in the U.S.
The CASCADE study in the U.K. explored correlations between biomarkers and risk stratification categories to help predict the subsets of COVID-19 pneumonia patients who have a higher propensity to deteriorate clinically to more severe disease
Nomacopan Manufacturing

Significantly increased the total yield of nomacopan (more than five-fold) with a new manufacturing process
References:

Tedbirt B, et al., JAMA Dermatol. 2021 Apr 1;157(4)
Liao DS, et al. Ophthalmology. 2020 Feb;127(2)
Jaffe GJ et al. Ophthalmology. 2021 Apr;128(4)
Sasaki F et al. JCI Insight. 2018 Sep 20;3(18)
Full Year 2021 Financial Results

At December 31, 2021, the Company had cash of approximately $9.4 million, compared to cash of approximately $14.1 million at December 31, 2020.
In March 2022, Akari entered into an agreement with Paulson Investment Company, LLC to serve as placement agent in connection with a registered direct offering and sold approximately 7.4 million of the Company’s ADSs for gross proceeds of approximately $8.9 million.
In December 2021, Akari entered into an agreement with Paulson Investment Company, LLC to serve as placement agent in connection with a registered direct offering and sold approximately 4.3 million of the Company’s ADSs for gross proceeds of approximately $6.0 million.
In July 2021, Akari closed a private placement of approximately $12.3 million in gross proceeds by issuing approximately 7.9 million of the Company’s ADSs.
Research and development (R&D) expenses for full year 2021 were approximately $9.1 million, as compared to approximately $8.8 million for full year 2020.
General and administrative expenses for full year 2021 were approximately $8.1 million, as compared to approximately $9.2 million for full year 2020. This decrease was primarily due to a one-time non-cash financing expense of approximately $900,000 in 2020 related to the 2020 Purchase Agreement with Aspire Capital.
For full year 2021, total other loss was approximately $210,000 as compared to total other income of approximately $899,000 for full year 2020. This change was primarily due to the accounting reclassification of warrant liabilities to shareholders’ equity as of December 2020.
Net loss for the full year 2021 was approximately $17.4 million, as compared to net loss of approximately $17.1 million for full year 2020.
A copy of the Company’s Annual Report on Form 20-F for the year ended December 31, 2021 will be filed with the Securities and Exchange Commission and posted on the Company’s website at View Source

On May 16, 2022 Promontory Therapeutics Inc., a clinical stage pharmaceutical company advancing small molecule immunotherapies in oncology, reported the appointment of Johan Baeck, MD, as Executive Vice President and Chief Medical Officer (Press release, Promontory Therapeutics, MAY 16, 2022, View Source [SID1234615802]). Dr. Baeck joins Promontory Therapeutics from Jounce Therapeutics where he served as Senior Vice President, Clinical Development and Medical Affairs.

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Joseph F. O’Donnell, MD, who previously served as Chief Medical Officer, will remain with Promontory Therapeutics and assume the role of Senior Medical Director focusing on patient eligibility, enrollment and clinical case management.

"We are especially pleased to welcome Dr. Baeck to the Promontory team. His extensive clinical development and medical affairs experience with both large pharmaceutical and smaller biotech companies complements our growth strategy," said Promontory President and Chief Executive Officer Robert Fallon. "In addition, Dr. Baeck’s strong background in immuno-oncology fits well with our focus on small molecule immunotherapy as we advance our lead agent, PT-112, in clinical trials for treating multiple cancer types, including prostate and lung cancers, and the rare disease of thymoma."

"I am excited to be part of a great group of dedicated, smart and driven people at Promontory," said Dr. Baeck. "The company is operating within the heart of the immuno-oncology field and new approaches will favor modalities with novel I-O mechanisms and single agent anti-cancer activity such as Promontory’s immunogenic cell death inducer, PT-112. The company is poised to make a major impact in the field."

Dr. Baeck completed his Medical Degree in Leuven, Belgium and was a practicing physician in Belgium before transitioning to the pharmaceutical industry. After many years with Abbott Laboratories and Novartis in key commercial, clinical development and medical affairs roles, as well as with smaller biotechs, he joined Immunocore as VP and Global Head of Medical Affairs and later Jounce Therapeutics. He has published in the immuno-oncology field and frequently speaks on recent I-O developments at key medical meetings.

On May 16, 2022 Emergent BioSolutions Inc. (NYSE: EBS) reported that it has entered into a definitive agreement with Chimerix, Inc. (NASDAQ: CMRX), to acquire Chimerix’s exclusive worldwide rights to TEMBEXA (brincidofovir), the first antiviral approved by the U.S. Food and Drug Administration (FDA) for all age groups for the treatment of smallpox (Press release, Emergent BioSolutions, MAY 16, 2022, View Source [SID1234614587]). TEMBEXA was approved in June 2021 and is indicated for the treatment of human smallpox disease in adult and pediatric patients, including neonates.

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"The addition of TEMBEXA to Emergent’s portfolio of medical countermeasures builds upon our core capabilities and leverages our long and successful history partnering with the U.S. government to address dangerous public health threats," said Robert G. Kramer, president and CEO of Emergent. "It exemplifies our thoughtful M&A strategy as part of our 2024 growth plan and positions us better to deliver value for our shareholders."

"This transaction expands and further diversifies our medical countermeasures business with the addition of a small molecule therapeutic that aligns with the government’s smallpox preparedness strategy," said Paul Williams, SVP government/MCM business at Emergent. "It is expected to be accretive upon first product delivery under the anticipated BARDA contract within three to six months from closing."

Transaction Details
Under the terms of the agreement, Emergent will pay Chimerix a $225 million one-time upfront payment in cash upon closing and up to a total of $100 million in milestone payments contingent on the potential exercise by the U.S. government of procurement options following the base period. The closing payment and the milestone payments may be adjusted based on the actual procurement value. The terms also include sales-based royalties contingent on future potential worldwide procurement during the exclusivity period of TEMBEXA on a market-to-market basis. Chimerix remains eligible to receive a portion of the regulatory milestone payments associated with the license to SymBio Pharmaceuticals Ltd. for indications other than orthopox infections.

Emergent anticipates that the transaction will be funded using currently available funds.

Closing Conditions
This transaction is subject to customary closing conditions, including expiration or early termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended (HSR Act).

The transaction is further conditioned on the execution of an anticipated procurement contract between Chimerix and the Biomedical Advanced Research and Development Authority (BARDA) as well as receipt of any required consent from BARDA to a pre-novation agreement to be entered into with Emergent, upon which time Emergent would be poised to deliver the first shipment of TEMBEXA to the U.S. Strategic National Stockpile (SNS) upon completion of customary pre-shipment obligations. In December 2021, BARDA issued a sole source request for proposal (RFP) to procure up to 1.7 million treatment courses of TEMBEXA. Chimerix expects a BARDA procurement contract award as early as second quarter of 2022.

Subject to the satisfaction or waiver of the closing conditions, the companies expect the transaction to close as early as the end of the second quarter of 2022.

ABOUT TEMBEXA
TEMBEXA is an oral antiviral formulated as 100 mg tablets and 10 mg/mL oral suspension dosed once weekly for two weeks. TEMBEXA is indicated for the treatment of human smallpox disease in adult and pediatric patients, including neonates. TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease.

In June 2021, the FDA approved TEMBEXA tablets and oral suspension for the treatment of smallpox. TEMBEXA is approved for adult and pediatric patients and is the first and only smallpox therapy approved for neonates. The oral suspension formulation is particularly important for patients who have difficulty swallowing due to age or medical status. Please read full prescribing information here.

About Smallpox
Smallpox is a highly contagious disease caused by the variola virus. Historically, smallpox was one of the deadliest diseases in history with a case fatality rate of approximately 30%. Despite successful eradication of smallpox in the 1970s, there is considerable concern that variola virus could reappear, either through accidental release or as a weapon of bioterrorism. According to the U.S. Centers for Disease Control and Prevention (CDC), variola virus is ranked in the highest risk category for bioterrorism agents (Category A) due to its ease of transmission, high mortality rate, and potential to cause public panic and social disruption. Based on a recent report – The Department of Health and Human Services Fiscal Year 2023 Public Health and Social Services Emergency Fund Justification of Estimates for Appropriations Committee – smallpox remains a threat of high concern to both the domestic and international community. BARDA’s goal is to ensure adequate vaccine supply for all Americans, including special populations, and to make available at least two different therapeutic agents as recommended by the National Academy of Medicine of the National Academies of Sciences, Engineering, and Medicine.