On May 1, 2023 Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biotechnology company developing advanced therapies for autoimmune and inflammatory diseases, reported financial results and highlights for the full year ended December 31, 2022, as well as recent company updates (Press release, Akari Therapeutics, MAY 1, 2023, View Source [SID1234630750]). Akari’s lead asset is investigational nomacopan, a novel bispecific inhibitor of both complement C5 and leukotriene B4 (LTB4). Nomacopan is currently in a Phase 3 clinical trial for pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA). Long-acting PAS-nomacopan is in pre-clinical development as a potential treatment for geographic atrophy (GA).

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"Nomacopan’s distinctive dual mechanism of action against two key proinflammatory mediators, C5 and LTB4, we believe has blockbuster potential with the versatility to take the complement inhibitor category to the next level across multiple rare diseases and mass markets," said Rachelle Jacques, Akari President and CEO. "During the last twelve months, Akari has made significant progress in realizing the promise of this novel asset by advancing to the registrational part of the Phase 3 clinical trials in pediatric HSCT-TMA and toward a regulatory filing for PAS-nomacopan to begin clinical trials in GA in the first half of 2024."

Full Year 2022 Highlights and Recent Updates
Phase 3 clinical trials of nomacopan in pediatric hematopoietic stem cell transplant-related thrombotic microangiopathy (HSCT-TMA)

Thrombotic microangiopathy (TMA) is a rare complication that can occur following a stem-cell transplant in adults or children; blood clots that develop in small blood vessels and capillaries can lead to multi-organ failure and death
There are no approved therapies to treat HSCT-TMA; across adults and children with severe HSCT-TMA, the mortality rate is estimated to be 80%
Complement activity is known to be implicated in moderate-to-severe HSCT-TMA with sC5b-9 and CH50 identified as key markers of disease; LTB4, which is also inhibited by nomacopan, may also be implicated by causing uncontrolled functioning of certain immune cells (such as neutrophils) that may lead to inflammation, tissue damage, and development of thrombosis
Akari accelerated the Phase 3 clinical trial of nomacopan for treatment of pediatric HSCT-TMA toward the portion of the study that is designed to generate the safety and efficacy data needed to support potential regulatory filings for marketing approval; enrollment in the pivotal portion is expected to begin by the end of 2023
In November 2022, the FDA granted the Rare Pediatric Disease Designation to nomacopan for the treatment of pediatric HSCT-TMA
The FDA Rare Pediatric Disease Designation is a recognition of the significant need that exists for approved treatments in rare pediatric diseases and is intended to encourage development of these treatments; the designation is an important addition to the Orphan Drug and Fast Track designations previously granted by the FDA for nomacopan in pediatric HSCT-TMA
With the Rare Pediatric Disease Designation, a sponsor who receives an approval of a new drug application (NDA) or biologics license application (BLA) is eligible for a Priority Review Voucher (PRV) to either redeem for priority review of a subsequent marketing application for a different product or sell to a third party
In the past year, other companies sold PRVs to third parties for prices ranging from $95 million to $110 million
A case study of the first patient to complete treatment in the Phase 3 clinical study of nomacopan in pediatric HSCT-TMA was presented as a late-breaker at the Transplantation & Cellular Therapy Tandem Meetings on February 16 and as a poster presentation at the European Society for Blood and Marrow Transplantation (EBMT) 49th Annual Meeting on April 23.
A 6-year-old male patient with severe HSCT-TMA was enrolled in the Phase 3 Part A clinical trial, and began treatment with a single age- and weight-based ablating dose of nomacopan followed by maintenance dosing for 21 days
Pharmacodynamic data demonstrated that the patient’s sC5b-9 had normalized and CH50 was reduced by >95% within the first 24-48 hours after initiating treatment
Treatment continued for 46 days until the patient’s urine protein creatinine ratio was corrected for ≥28 days; gut pathology and thrombocytopenia were resolved
The patient was discharged from the hospital and no adverse events related to nomacopan were experienced during the treatment period
Akari added a new pipeline program that will develop nomacopan for HSCT-TMA in adults
The adult HSCT-TMA population is >10 times the size of the pediatric population
There are no approved therapies for the treatment of adult HSCT-TMA
Study enrollment for the adult program is expected in 2024
Pre-clinical development of long-acting PAS-nomacopan for geographic atrophy (GA) which is estimated to affect the vision of approximately one million people in the U.S. alone

GA is a chronic progressive degeneration of the macula in the aging eye leading to lesions on the outer retina that can cause irreversible vision loss
There is currently one FDA-approved therapy for treatment of GA and one filed with the FDA, both are complement inhibitors; treatments are administered to patients through monthly or every-other-month needle injections into the eye (intravitreal injections/IVTs)
Frequent needle injections into the eye are a source of fear, discomfort, disruption for patients and has been shown to decrease patient compliance with optimal dosing regimens
Long-acting PAS-nomacopan has the potential to deliver efficacy benefits of complement inhibition using a fraction of the annual doses/injections of approved and late-stage complement-only inhibitors for GA
Sight-threatening choroidal neovascularization (CNV) is a safety risk associated with currently approved and late-stage complement-only inhibitors used for the treatment of GA; CNV is typically treated chronically with anti-VEGF intravitreal injections
CNV is an overdevelopment of blood vessels and leakage in the retina that can significantly damage sight; LTB4 can cause the overexpression of VEGF-A, which can stimulate overproduction of the cells that form the inner layer of blood vessels, leading to CNV
The dual mechanism of PAS-nomacopan may offer the well-understood benefits of intravitreally-administered complement C5 inhibition in slowing the progression of GA lesions, while also providing LTB4 inhibition that also has the potential to help prevent VEGF-A overexpression, reducing the likelihood of CNV and the need for chronic IVT injection or therapies to control CNV
During the past year, Akari significantly advanced the pre-clinical development of long-acting PAS-nomacopan as a potential treatment for GA; the program is on track to submit an Investigational New Drug (IND) application to the FDA in the first half of 2024 for clinical trials
Chemical Manufacturing and Controls (CMC)

U.K, and Poland regulatory authorities –Medicines & Healthcare products Regulatory Agency (MHRA) and Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (URPL) have approved the use of a new, approximately 5X higher-yielding manufacturing process (compared to the previous process) in the pivotal Phase 3 clinical trial of nomacopan in pediatric HSCT-TMA
Patents/Intellectual Property (IP)

A composition of matter patent application was filed on long-acting PAS-nomacopan versions, which, if granted, provides patent protection until 2042
Akari continues to secure IP for lead asset nomacopan in pipeline programs beyond current priority programs in preparation for future development by the company, licensing or partnering
In April 2023, the European Patent Office granted a patent for nomacopan in the treatment of autoimmune blistering diseases (including bullous pemphigoid)
Management Team

• The Akari management team was expanded with industry veterans John Neylan, M.D., Executive Vice President and Chief Medical Officer, and Melissa Bradford Klug, Chief Operating Officer

Full Year 2022 Financial Results

At December 31, 2022, the Company had cash of approximately $13.2 million, compared to cash of approximately $9.4 million at December 31, 2021
Since the beginning of 2022, Akari entered into agreements with Paulson Investment Company, LLC as well as A.G.P./ Alliance Global Partners to serve as placement agents in connection with a total of three registered direct offerings for total gross proceeds of approximately $27.7 million
Research and development expenses for full year 2022 were approximately $9.6 million, as compared to approximately $9.1 million for full year 2021. The change was the net impact of multiple factors. The Company’s research and development expenses increased due to the receipt of a lower tax credit in 2022 as compared to 2021 and increased maintenance and renewal costs for our patents. These increases were partially offset by decreases in staffing costs and decreases in clinical trial costs resulting from the Company’s decision to close the BP trial in August 2022.

General and administrative expenses for full year 2022 were approximately $13.5 million, as compared to approximately $8.1 million for full year 2021. The increase was due to several factors including hiring of a new CEO and COO, severance paid to our departing CEO, issuance costs from our September 2022 registered direct offering, and external costs for consulting personnel, investor relations and corporate communications.
For full year 2022, total other income was approximately $5.3 million as compared to total other expense of approximately $0.2 million for full year 2021. The change was primarily attributed to the classification of our warrants, issued as part of the September 2022 offering, which are accounted for as liabilities and subject to revaluation at each reporting period.
Net loss for the full year 2022 was approximately $17.8 million, as compared to net loss of approximately $17.4 million for full year 2021