On December 5, 2021 Isofol Medical AB (publ) (Nasdaq Stockholm: ISOFOL), reported on December 3 that the ongoing phase III study AGENT will not reach 300 PFS events with current censoring rules based on FDA decision (Press release, Isofol Medical, DEC 5, 2021, View Source [SID1234596455]). Following this announcement, Isofol invites investors, analysts, and media to an audiocast (in English) with a Q&A-session on December 6, at 08:00 a.m. CET.

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The presentation will be held by Isofol’s CEO Ulf Jungnelius and CMO Roger Tell in English and will conclude with a Q&A session. Questions can be asked on the telephone conference or in written form through the webcast. No preregistration is needed.

Date and time
December 6, 2021, at 08:00 a.m. CET

Webcast link
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Phone number
Call in details will be made available at the following link in good time before the start of the presentation:
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The presentation will also be available on Isofol’s website after the broadcast.

On December 4, 2021 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that positive final data from a phase II clinical study of paxalisib as first line therapy in patients with glioblastoma (NCT03522298) (Press release, Kazia Therapeutics, DEC 4, 2021, View Source [SID1234596461]). The results confirm the previously reported safety and efficacy profile with paxalisib in this high unmet need disease.

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Key Points

The study recruited 30 patients with newly diagnosed glioblastoma and unmethylated MGMT promotor status, a genetic profile which confers primary resistance to temozolomide, the only existing FDA-approved drug treatment for first line treatment.
60mg once daily was identified as the maximum tolerated dose (MTD) and selected for future studies.
Median overall survival (OS) in the intent-to-treat (ITT) population (n=30) was 15.7 months (11.1 – 19.1), which compares very favourably to 12.7 months historically reported with temozolomide in this patient group.1
Median progression-free survival (PFS) in the ITT population was 8.4 months (6.6 – 10.2), representing a substantial increment over the comparable figure of 5.3 months associated with temozolomide.
In the modified ITT (mITT) population (n=27), which includes only those patients evaluable for efficacy, OS increased to 15.9 months (12.8 – 19.1).
The safety profile of paxalisib was highly consistent with previous clinical studies: hyperglycaemia, oral mucositis, and skin rash were among the most common drug-related toxicities.
Kazia expects to receive a final clinical study report in 1Q CY2022 and intends to seek publication of these data in a peer-reviewed scientific journal thereafter.
Kazia CEO, Dr James Garner, commented, "We are delighted to report positive final data from the completed phase II study of paxalisib. The data continue to demonstrate a clear efficacy signal and favourable safety profile, suggesting a meaningful advantage over temozolomide, the existing standard of care, and validating our decision last year to join the GBM AGILE pivotal study. We have gleaned invaluable insights from this trial, and we are tremendously grateful to the investigators and to the patients who participated. Our task now, as we move rapidly toward a potential marketing authorization, is to confirm and quantify the benefit associated with paxalisib in glioblastoma patients. This indeed is the focus of our participation in GBM AGILE, which commenced recruiting to the paxalisib arm in January 2021. We are increasingly also exploring additional patient populations for which a brain penetrant PI3K/mTOR inhibitor may provide significant advantages over the standard of care."

Professor Patrick Wen, Principal Investigator at Dana Farber Cancer Institute, commented "We are pleased to see the phase II study of paxalisib successfully completed. This data supports the inclusion of paxalisib in the GBM AGILE study, which has recently expanded to Canada. Glioblastoma remains a disease in urgent need of new therapeutic options, and we look forward to seeing further data for paxalisib from GBM AGILE in due course."

Clinical Trial Design

The phase II study of paxalisib was an adaptive trial, conducted in two stages. The first stage sought to determine the most appropriate dose in newly diagnosed patients. The second stage was intended to provide additional information on dosing and to seek a preliminary efficacy signal in order to de-risk transition to a larger, pivotal study.

Consistent with these objectives, the primary objective of the study was to evaluate the safety and tolerability of paxalisib in patients with newly diagnosed glioblastoma. The secondary objectives included typical pharmacokinetic parameters, and efficacy endpoints including overall survival (OS) and progression-free survival (PFS).

The phase II study was conducted in 30 patients at six centres in the United States. It was a single arm study in which all patients received paxalisib as a monotherapy. As such, all data must be interpreted in the context of historical comparators. Specifically, Kazia has referred to the pivotal study of temozolomide, the only existing FDA-approved drug for this patient population. Such comparisons are always inexact, and this study was not designed either to precisely quantify the benefit associated with paxalisib or to demonstrate statistical significance. Rather, these are among the objectives of the ongoing GBM AGILE pivotal trial.

Next Steps

On the basis of earlier interim analyses of this study, Kazia made the decision in 4Q CY2020 to commence participation in the GBM AGILE pivotal study. This global trial recruited its first patient to the paxalisib arm in January 2021 and recruitment is ongoing. Kazia provisionally expects indicative data in CY2023.

Seven other studies of paxalisib are ongoing in other forms of primary brain cancer and in various forms of cancer that has metastasized to the brain. The company is working with investigators to crystalise the timing of initial data read-outs from these studies. Kazia had expected at least two further read-outs by the end of CY2021. Clinicians have now indicated that data early in CY2022 is most likely. The company will continue to keep shareholders closely informed as it receives further feedback from investigators.

Having successfully concluded the phase II study in glioblastoma, the investigators are composing a manuscript for submission and publication to a peer-reviewed academic journal in 2022. Once the data has been more thoroughly analysed, Kazia expects to share further detail with investors as it becomes available.

On December 3, 2021 Henlius Biotech (Fosun) reported that bevacizumab biosimilar Hanbeitai, developed and manufactured by Henlius independently, has been approved by the National Medical Products Administration (NMPA) (Press release, Shanghai Henlius Biotech, DEC 3, 2021, View Source [SID1234605560]). It is indicated for the treatment of metastatic colorectal cancer (mCRC) and unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (nsNSCLC). Hanbeitai is the company’s fourth monoclonal antibody (mAb) approved in China, following rituximab biosimilar Hanlikang, trastuzumab biosimilar Hanquyou (ZercepacⓇ in the EU), and adalimumab biosimilar Handayuan. The pipeline has been further replenished with widened indication coverage including hematological malignancies, solid tumors, auto-immune diseases, etc.

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Mr. Wenjie Zhang, Chairman, Executive Director, and CEO of Henlius, said, "We are excited to have Hanbeitai get approved as our fourth product. The credit goes to all the healthcare professionals, patients and regulatory authorities that have contributed to the studies of Hanbeitai. While maximizing the value of biosimilar drugs, we will continue advancing the clinical trial process of its combination with in-house immunotherapy products, such as serplulimab, and growing into a more innovative global biopharmaceutical company."

Mr. Jason Zhu, President of Henlius, said, "Lung cancer and colorectal cancer are ranked second and third with high incidence of cancers in the world, respectively. They are also ranked first and second in China, and there is a huge demand for treatment. The similarity studies showed no statistically significant difference in efficacy, and the safety are highly similar to the originator. It is believed that the approval of Hanbeitai will further improve the accessibility of bevacizumab and provide a high-quality option for patients with lung cancer and colorectal cancer."

Study showed Hanbeitai is highly similar to the originator, addressing significant unmet clinical needs

Hanbeitai was developed in accordance with the NMPA Technical Guidelines for the Development and Evaluation of Biosimilars (Tentative), and has received support from National Science and Technology Major Project in the 12th & 13th Five-Year Plans of China-Major New Drug Research & Development Project. The approval is mainly supported by a series of study data, including comparative pharmaceutical quality studies, comparative non-clinical studies, comparative clinical studies. Different from approved bevacizumab biosimilars in China, the Phase 3 study of Hanbeitai was conducted among Chinese patients with metastatic colorectal cancer (CRC), which helps to accumulate more clinical evidence and experience of bevacizumab in this patient population. The relevant Phase 3 clinical studies were published at the 23rd annual conference of Chinese Society of Clinical Oncology (CSCO) for the first time and awarded an "outstanding study paper". And then the Phase 3 results were published on the world-renowned journal BioDrugs. The Phase 1 clinical study results were also published on Cancer Chemotherapy and Pharmacology.

According to GLOBOCAN data, lung cancer (LC) is the second commonly diagnosed cancer globally and accounts for 11.4% of the global cancer incidence in 2020. It is estimated that 810,000 people are diagnosed with LC in China, and LC is the first leading cause of cancer incidence and mortality. NSCLC is the most common type of LC, accounting for 80%-85%. The incidence rate of CRC ranks second among all malignant tumours in China, with over 550,000 new cases in 2020. Clinical studies showed that adding bevacizumab to traditional chemotherapies can significantly delay disease progression and prolong survival for patients with mCRC and is one of the standards of care for advanced CRC.

By specific binding with vascular endothelial growth factor (VEGF), Hanbeitai can block the interaction between VEGF and its receptors. This will inhibit tumour angiogenesis, which is essential for the growth and metastases of tumour. The originator has been approved for CRC, LC, glioblastoma, hepatocellular carcinoma (HCC), ovarian cancer, cervical cancer in China. For global the indications also include renal cell carcinoma and breast cancer, and so on. However, there are still significant unmet needs due to drug accessibility in China. Going beyond, Henlius will explore more indications to benefit more patients.

Exploring more therapies

Building upon the advantages in the field of broad-spectrum anti-tumour of bevacizumab, Henlius is actively developing combo therapies of Hanbeitai and its anti-PD-1 mAb serplulimab for the treatment of various solid tumours. Clinical studies of this combo have been conducted in first-line nsNSCLC and first-line CRC. The first-line nsNSCLC study has entered the pivotal Phase 3 stage. The CRC Phase 2 clinical trial is on track. With the continuous exploration, Henlius aims to benefit patients with immuno-oncology mAbs combination therapies as early as possible, further delaying the disease progression and improving the survival status of patients with mCRC.

According to the requirements of ophthalmic drugs, Henlius is also developing a new ophthalmic preparation product, HLX04-O (recombinant anti-VEGF humanised monoclonal antibody injection), based on Hanbeitai, through optimizing the prescription, specifications and production processes of Hanbeitai, with active ingredients remaining unchanged. It is intended to be used for the treatment of wet age-related macular degeneration (wAMD). In the first half of 2021, HLX04-O has been approved to carry out Phase 3 clinical trials in Australia, the United States, Singapore, and EU countries such as Latvia, Hungary and Spain. In addition, the first patient was dosed in a HLX04-O Phase 3 clinical trial in China for the treatment of wAMD.

Looking forward, with its core values of "Affordable Innovation, Reliable Quality", Henlius is actively accelerating the R&D and commercialisation of more biologics and enriching innovative target layouts. What’s more, the company will continue developing a forward-looking presence in bispecific antibodies and antibody-drug conjugates (ADC), and bringing more high-quality and affordable therapies to patients worldwide.

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.

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.

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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!