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Akari Therapeutics Reports Third Quarter 2021 Financial Results and Highlights Recent Clinical Progress

On December 3, 2021 Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where complement (C5) and/or leukotriene (LTB4) systems are implicated, reported its financial results for the third quarter of 2021 and recent clinical progress (Press release, Akari Therapeutics, DEC 3, 2021, View Source [SID1234596634]).

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Akari’s two lead programs, in BP and pediatric HSCT-TMA, are in Phase III clinical development and both have been granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA). The Company also has earlier stage programs addressing ophthalmology and pulmonary diseases.

"During 2021, Akari has been very active and focused on the launch of our two orphan Phase III programs for BP and HSCT-TMA as well as the further development of our lung and eye franchises based on new formulations of our lead asset, nomacopan," said Clive Richardson, Chief Executive Officer of Akari Therapeutics. "We now expect multiple readouts across our key ongoing and proposed programs over the next 12-18 months."

Clinical highlights

Phase III clinical trial in patients with bullous pemphigoid

BP is a severe autoimmune blistering disease of the elderly with no specific approved treatments.

The Company has opened the first sites for its Phase III study of nomacopan for the treatment of BP and anticipates commencing treatment by the end of 2021.
The FDA and the European Medicines Agency (EMA) have both granted Orphan Drug Designation for nomacopan for the treatment of BP, and the FDA has granted Fast Track designation to nomacopan in BP.
The Company is considering additional opportunities to expand into other dermatological conditions where both complement C5 activation and LTB4 are believed to have key roles in driving the disease pathology including hidradenitis suppurativa and other pemphigoid diseases.
Phase III clinical trial in patients with pediatric HSCT-TMA

HSCT-TMA is a severe disease in pediatric patients with an approximately 80% mortality rate in patients with proteinuria and elevated terminal complement activity. There are no approved treatments.

Phase III study in pediatric HSCT-TMA is now enrolling and treating patients.
The FDA has granted both Fast Track and Orphan Drug Designations for nomacopan for the treatment of pediatric HSCT-TMA.
Success in pediatric HSCT-TMA would provide opportunities to expand into adult HSCT-TMA and related TMA-like diseases where complement and LTB4 are believed to have important roles such as atypical hemolytic uremic syndrome, systemic lupus erythematosus and anti-phospholipid syndrome.
OTHER CLINICAL PROGRAMS

Akari Therapeutics is also pursuing other earlier stage programs that are primarily focused on large disease areas with high unmet need and where complement and leukotriene pathways are implicated. For these programs, the Company is using alternative formulations to the subcutaneous delivery of nomacopan including topical, nebulized or long-acting engineered forms, which provide an opportunity for separate partnering options.

Ophthalmology program

Recent publications (Eskandarpour et al 2020 and 2021) support a potential therapeutic role for longer acting PAS-nomacopan in sight-threatening retinal diseases given its inhibition of both complement and vascular endothelial growth factor (VEGF) via its inhibition of LTB4. This unique combination may be particularly relevant to geographic atrophy (GA)/dry AMD where complement is a key treatment target as evidenced by Phase II and III data from Apellis and Iveric Bio, and VEGF inhibition by nomacopan may prevent neo vascularisation, which has been seen in some GA patients treated with other complement inhibitors.
In order to increase the interval between intravitreal injections into the back of the eye, the program is being advanced with PAS-nomacopan, an engineered form of nomacopan with an extended half-life. Data from pharmacokinetics (PK) studies with PAS-nomacopan to estimate injection interval in the back of the eye are expected by the end of 2021.
Animal models described in a recent publication (1) highlight that nomacopan eye drops reduced inflammation more than both standard treatments, cyclosporin and the steroid dexamethasone in a model of allergic eye disease.
Eskandarpour 2021, Allergy: Allergic eye disease: blocking LTB4/C5 in vivo suppressed disease and Th2 & Th9 cells
Lung program

An observational study sponsored by Akari in COVID-pneumonia showed that elevated levels of C5a, C5b9 and LTB4 were present in COVID-pneumonia patients and that the levels of C5a (p = 0.001) and C5b9 (p=0.019), which are potential biomarkers for disease progression, rose significantly in patients that worsened. These findings align with a prior, separate Akari-sponsored observational study in chronic obstructive cardiopulmonary disease (COPD) patients that demonstrated that the level of C5a was significantly correlated with the severity of the exacerbations (p=0.01).
Akari is investigating the PK of inhaled nomacopan in the lung and a proof of principle study in exacerbating COPD patients to further evaluate the impact of inhibiting C5 and LTB4 with nomacopan.
The COVID-pneumonia observational findings are being further evaluated to explore the potential role of biomarkers in identifying the most appropriate COVID-pneumonia patients who might respond to nomacopan.
Trauma

The damaging role of both C5 and LTB4 has been implicated in trauma and Akari is exploring both blast injury and hemorrhagic shock with the United States Army Institute of Surgical Research (USAISR) where nomacopan has been shown to improve survival in pre-clinical studies. In addition, a separate new collaborative study in traumatic brain injury and subarachnoid hemorrhage in man is being initiated in the UK.
Histamine inhibitor

Votucalis, a molecule with a similar origin to nomacopan, has a unique mode of action by binding directly to histamine and preventing the activation of all four histamine G-protein coupled receptors. Ongoing work in collaboration with Durham and Newcastle Universities is focused on expanding the Company’s existing dermatology franchise with initial skin penetration data indicating a potential opportunity for topical delivery.
Third Quarter 2021 Financial Results

As of September 30, 2021, the Company had cash of approximately $13.4 million, compared to cash of approximately $14.1 million at December 31, 2020. 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.
In September 2020, Akari entered into a securities purchase agreement with Aspire Capital Fund, LLC (Aspire Capital) whereby Aspire Capital is committed to purchase up to an aggregate of $30.0 million of the Company’s ADSs. During the nine months ended September 30, 2021, the Company sold to Aspire Capital ordinary shares for gross proceeds of $2.0 million. As of September 30, 2021, $22.0 million of the original purchase commitment remains available.
Research and development (R&D) income for the third quarter 2021 were approximately $0.4 million, as compared to approximately $1.6 million in the same quarter the prior year. This decrease in income was primarily due to lower R&D tax credit received for the 2020 tax year and higher expenses incurred for clinical trials in the third quarter 2021.
General and administrative expenses for the third quarter 2021 were approximately $1.9 million, as compared to approximately $1.8 million in the same quarter the prior year.
For the third quarter 2021, total other income was approximately $12,000 as compared to total other income of approximately $1.2 million in the third quarter of 2020. This change was primarily due to the accounting reclassification of warrant liabilities to shareholders’ equity as of December 2020.
Net loss for the third quarter 2021 was approximately $1.5 million, as compared to net income of approximately $0.9 million for the period of 2020. This decrease was primarily due to the aforementioned lower R&D income as well as lower total other income.

SABCS 2021: Genome-based Data for Breast Cancer Risk and Treatment

On December 3, 2021 Crescendo Bioscience reported In the breast cancer research and clinical communities, one of the biggest events of the year is the San Antonio Breast Cancer Symposium (Press release, Crescendo Bioscience, DEC 3, 2021, View Source [SID1234596472]). It’s a place where leaders in the field come together to share the latest advances, discoveries, and validation studies relevant to the treatment of breast cancer.

At this year’s meeting, Myriad Genetics team members will be presenting two posters reporting results from studies that showcase the importance of genetic testing and precision medicine as integral components of both breast cancer treatment recommendations and risk assessment.

Here’s a look at some highlights from each poster.

Identifying homologous recombination deficiency in breast cancer: genomic instability score thresholds differ in breast cancer subtypes P5-13-09 Poster Session 5, December 10, 2021, 7:00 a.m. – 8:30 a.m. (CST)

Presenter: Kirsten Timms

This poster, from researchers at Myriad Genetics, the Mayo Clinic, Johns Hopkins School of Medicine, Indiana University, and University College Cork, describes the results of a study designed to assess the differences in genomic instability score (GIS) thresholds for triple-negative breast cancer and estrogen receptor-positive breast cancer. The team used the GIS for ovarian cancer as a comparator to guide the identification of potential candidates for treatment with PARP inhibitors. GIS markers highlight the presence of homologous recombination-deficient tumors that may benefit from DNA damaging agents such as PARP inhibitors. Researchers analyzed more than 1,000 tumors and determined that different cancers require different GIS thresholds, and that more inclusive levels could allow more people to receive beneficial PARP treatment.

Integration of an ancestry-inclusive polygenic risk score with the Tyrer-Cuzick breast cancer risk model

P2-11-21 Poster Session 2, December 8, 2021, 5:00 p.m. – 6:30 p.m. (CST)

Presenter: Elisha Hughes

Based on a collaborative team from Cleveland Clinic, University of Pennsylvania, Dana-Farber Cancer Institute, and other institutions, this study validates the integration of an ancestry-inclusive breast cancer polygenic risk score with a clinical and family history-based model in the development of a risk assessment tool for breast cancer. The team reviewed data for nearly 69,000 women, looking for cases where risk would have been reclassified based on the addition of genomic information. They found that risk stratification improved with the incorporation of a polygenic risk score, allowing for personalized five-year and lifetime risk estimates for women of all ancestries.

These posters reflect Myriad Genetics’ ongoing commitment to improve risk prediction and treatment for breast cancer so that women can be empowered to take charge of their health. We congratulate all of the scientists and clinicians who participated in these important studies!

I-Mab Announces First Two Patients Dosed in U.S. Phase 2 Combination Trial of Uliledlimab with Atezolizumab in Patients with Selected Advanced Solid Tumors

On December 3, 2021 I-Mab (the "Company") (Nasdaq: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel biologics, reported that the first two patients have been dosed in the U.S. phase 2 dose expansion clinical study of its proprietary CD73 antibody uliledlimab (also known as TJD5) in combination with atezolizumab (Tecentriq) in patients with ovarian cancer and other selected advanced or metastatic solid tumors (Press release, I-Mab Biopharma, DEC 3, 2021, View Source [SID1234596467]).

Uliledlimab is a novel, humanized CD73 antibody that binds to a unique epitope and completely inhibits CD73, reversing the adenosine-mediated immunosuppression in the tumor microenvironment and inhibiting tumor growth. CD73 has been implicated in immune escape by cancer cells and may contribute to tumor resistance to checkpoint immunotherapies, such as PD-(L)1 inhibitors. Uliledlimab has the unique property of not exhibiting the "hook effect," which potentially increases the therapeutic window and improves clinical efficacy compared to other CD73 antibodies. The phase 1 clinical data has demonstrated favorable safety and promising clinical activity for the combination of uliledlimab and atezolizumab in patients with advanced cancers.

This U.S. phase 2 dose expansion study is a multi-center, open-label trial that will explore the clinical activities of uliledlimab in combination with atezolizumab and potential biomarkers in patients with selected advanced or metastatic solid tumors. This clinical study will include a dose expansion cohort of patients with ovarian cancer resistant to platinum therapy, and a biomarker-driven "basket" cohort of patients with head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), gastrointestinal cancer, triple-negative breast cancer (TNBC), or ovarian cancer with PD-L1 expression ³ 1%. Uliledlimab is undergoing clinical development in China and the U.S. in parallel with different focus of targeted patient populations. The clinical data from both geographies will be leveraged to accelerate global develoment towards pivotal clinical study in patients with selected solid tumor types.

"Uliledlimab has unique pharmacological properties which position it as the next-generation immuno-oncology agent," said Dr. Joan Shen, CEO of I-Mab. "We hope the data from this study will accelerate the clinical development towards registration and to address the needs of patients with immune checkpoint resistance."

Based on the results of the phase 1 study, the Company was able to determine the Recommended Phase 2 Dose (RP2D) which it is using for this phase 2 study. Upon completion of the phase 1 study earlier this year, I-Mab decided to conduct subsequent studies in the U.S under its own management.

I-Mab is also conducting a China phase 2 cohort expansion study of uliledlimab in combination with toripalimab (TUOYI), a PD-1 inhibitor, in patients with advanced or metastatic cancers who are refractory to or intolerant of all available therapies.

About Uliledlimab (TJD5)

Uliledlimab (TJD5) is a differentiated, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine. Adenosine in turn binds to adenosine receptors on relevant immune cells and inhibits anti-tumor immune responses in tumor microenvironment. Uliledlimab is expected to offer clinical benefit by suppressing tumor growth in concert with checkpoint therapies such as PD-(L)1 antibodies. Uliledlimab is effective in anti-tumor activities through a unique intra-dimer binding, leading to differentiated and favorable functional properties as evident in preclinical studies.

Galapagos increases share capital through subscription right exercises

On December 3, 2021 Galapagos NV (Euronext & NASDAQ: GLPG) reported a share capital increase arising from subscription right exercises (Press release, Galapagos, DEC 3, 2021, View Source [SID1234596466]).

Galapagos issued 22,600 new ordinary shares on 3 December 2021, for a total capital increase (including issuance premium) of €578,700.00.

Pursuant to the subscription right exercise program of Galapagos’ management board, members of the management board automatically are committed to exercise a minimum number of subscription rights, subject to certain conditions. In accordance with the rules of this program, one management board member exercised 5,000 subscription rights.

In accordance with Belgian transparency legislation1, Galapagos notes that its total share capital currently amounts to €354,582,005.11, the total number of securities conferring voting rights amounts to 65,552,721, which is also the total number of voting rights (the "denominator"), and all securities conferring voting rights and all voting rights are of the same category. The total number of rights (formerly known as warrants) to subscribe to not yet issued securities conferring voting rights is (i) 8,709,735 subscription rights under several outstanding employee subscription right plans, which equals 8,709,735 voting rights that may result from the exercise of those subscription rights, and (ii) one subscription right issued to Gilead Therapeutics to subscribe for a maximum number of shares that is sufficient to bring the shareholding of Gilead and its affiliates to 29.9% of the actually issued and outstanding shares after the exercise of the subscription right. Galapagos does not have any convertible bonds or shares without voting rights outstanding.

Isofol Medical AB (publ) will not reach 300 PFS events in the AGENT study with current censoring rules based on FDA decision

On December 3, 2021 Isofol Medical AB (publ) (Nasdaq Stockholm: ISOFOL), reported that the U.S. Food and Drug Administration (FDA) denied a request from the company to adjust the analysis of the pivotal AGENT study’s secondary endpoint of progression-free survival (PFS) (Press release, Isofol Medical, DEC 3, 2021, View Source [SID1234596451]). However, the decision will not affect the study’s primary endpoint, objective response rate, previously agreed upon with the FDA. The secondary endpoint may have to be somewhat modified.

In the AGENT study, more patients than expected have proceeded to other treatments before they reached tumor progression (PFS). Isofol is blinded to the study data, and therefore it is not possible for Isofol to know whether the change is occurring in one or both treatment arms of the study, or the reason for patients proceeding to other treatments. However, the study’s Data Safety Monitoring Board has repeatedly reviewed the safety data of the study with no resulting changes. The consequence of the treatment change is that Isofol will be unable to reach its target of 300 PFS events with the current censoring rules.

Isofol requested that the censoring rules be adjusted in accordance with the ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines adopted by the FDA in 2021. However, during a "Type C" meeting the FDA denied the request and will analyze the study results based on the original censoring rules for the primary analysis of PFS. The decision may cause a delay of top-line results of arfolitixorin in advanced, metastatic colorectal cancer. Isofol is currently analyzing the options to address the feedback received from the FDA and what impact it will have on the PFS endpoint. However, the AGENT study’s primary endpoint of overall response rate (ORR) is not affected. The study is continuing according to plan.

"We had expected the FDA to accept our proposal to adjust the analysis in line with the new ICH guidelines. Our ongoing discussions with the FDA, including the additional opportunities for interaction that the new Fast Track Designation enables, are productive. We remain optimistic and hopeful that the AGENT study will have a positive outcome for the benefit of patients, their caregivers and our shareholders," said Ulf Jungnelius, CEO of Isofol.

This is information that Isofol Medical AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 20:15 CET on December 3, 2021.

About arfolitixorin

Arfolitixorin is Isofol’s proprietary drug candidate being developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. The drug candidate is currently being studied in a global pivotal Phase III study, AGENT. Arfolitixorin is the first and only immediately active folate and can potentially benefit more patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.

About the AGENT study

The Phase III AGENT study is a randomized, controlled, multi-centre study assessing the efficacy and safety of arfolitixorin, [6R]-5,10-methylene-THF acid (MTHF), compared to leucovorin, both used in combination with 5-FU, oxaliplatin, and bevacizumab, in first line metastatic colorectal cancer patients. Patients are randomized in a 1:1 ratio and the primary endpoint is overall response rate (ORR). The key secondary endpoints are progression free survival (PFS) and duration of response (DOR). Other secondary endpoints include overall survival (OS), number of curative metastasis resections, safety, and patient reported outcomes such as quality of life (QoL). Exploratory endpoints include pharmacokinetic (PK) measurements and level of gene expression of folate relevant genes in tumour cells. The study is designed to show superiority for arfolitixorin over leucovorin.

The study has involved approximately 90 clinics in the U.S., Canada, Europe, Australia and Japan. In December 2020, the last of the AGENT study’s 440 patients were recruited, which is the basis in the statistical analysis plan. Isofol is now focusing on completing the ongoing global AGENT study where the patients receive first-line standard treatment for metastatic colorectal cancer (mCRC) with either leucovorin or arfolitixorin. The company expects that top-line results of the AGENT study will be available during H1 2022. Further information about the study, including patient eligibility requirements, is available at www.clinicaltrials.gov id:NCT03750786.