On December 11, 2020 Bristol Myers Squibb (NYSE: BMY) reported that its wholly owned subsidiary, Celgene, and Cipla Limited (Cipla) have settled their litigation related to patents for REVLIMID (lenalidomide) (Press release, Bristol-Myers Squibb, DEC 11, 2020, View Source [SID1234572692]).

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As part of the settlement, the parties will file Consent Judgments with the United States District Court for the District of New Jersey that enjoin Cipla from marketing generic lenalidomide before the expiration of the patents-in-suit, except as provided for in the settlement, as described below.

In settlement of all outstanding claims in the litigation, Celgene has agreed to provide Cipla with a license to Celgene’s patents required to manufacture and sell certain volume-limited amounts of generic lenalidomide in the United States beginning on a confidential date that is some time after March 2022. For each consecutive twelve-month period (or part thereof), following the volume-limited entry date until January 31, 2026, the volume of generic lenalidomide sold by Cipla cannot exceed certain agreed-upon percentages. The specific volume-limited license date and percentages are confidential. In addition, Celgene has agreed to provide Cipla with a license to Celgene’s patents required to manufacture and sell an unlimited quantity of generic lenalidomide in the United States beginning no earlier than January 31, 2026.

Cipla’s ability to market lenalidomide in the U.S. will be contingent on its obtaining approval of an Abbreviated New Drug Application.

On December 11, 2020 Nextera reported that the Norwegian Research Council (NRC) has awarded a prestigious 15.7 MNOK grant funding to expand our NextCore platform with a novel T cell receptor (TCR) discovery pipeline (Press release, Nextera, DEC 11, 2020, View Source [SID1234575788]).

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The latest generation immuno-oncology (IO) therapies have shown a remarkable ability to treat and eventually cure cancer by evoking or grafting an anti-cancer immune response into patients. T cells are at the core of this immune response and they acquire this ability through their TCRs. Therefore, further improvements in harnessing IO therapy will critically depend upon the availability of clinically safe and potent TCRs.

"The NextCore phage display platform is uniquely equipped to address the unmet need in therapeutic TCR supply and development. This project is a natural expansion of our already strong T cell immunology focus in drug discovery, and gives Nextera a solid footprint in current and next generation cancer immunotherapies. The grant is instrumental for the initiation of this project, and represents a validation of Nextera’s commercial pathway." Geir Åge Løset, PhD, co-founder and Chief Executive Officer, Nextera AS, commented.

On December 11, 2020 Exact Sciences Corp. (NASDAQ: EXAS) reported the presentation of new data at the virtual 2020 San Antonio Breast Cancer Symposium (SABCS) building on the clinical value of the Oncotype DX Breast Recurrence Score test (Press release, Exact Sciences, DEC 11, 2020, View Source [SID1234572659]). These data highlight the role of the test in further individualizing treatment decisions in early breast cancer.

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"These latest presentations, including data from the RxPONDER trial, further highlight the unique value of the Recurrence Score result in providing critical information to personalize and improve the quality of treatment decisions in node-negative and node-positive early breast cancer," said Rick Baehner, MD, chief medical officer of Precision Oncology at Exact Sciences.

Five-year outcomes from ADAPT study show that not all clinically high-risk patients with node-negative or node-positive disease need chemotherapy

First efficacy results from the ADAPT study (4,691 patients) were presented at SABCS.[i]Patients were all considered candidates for chemotherapy by traditional parameters and were stratified using the Oncotype DX test and changes in the immunohistochemical prognostic marker Ki67 after three weeks of pre-operative anti-hormonal therapy. Patients with clinically high risk node-negative disease, and node-positive disease with up to 3 positive nodes, were treated with anti-hormonal therapy alone if the Recurrence Score result was 0–11 or if the Recurrence Score result was 12-25 with a Ki67 response. This group of patients had, regardless of their age, favorable outcomes with anti-hormonal therapy alone, with 5-year distant disease-free survival of 96%.

Another analysis from the ADAPT trial also presented at SABCS evaluated 864 breast cancer patients who received neoadjuvant chemotherapy primarily based on their Recurrence Score result.[ii] These results from a large neoadjuvant trial showed that the Recurrence Score result is a strong predictor of response to chemotherapy as assessed by the rate of pathologic complete response (no residual invasive tumor).

ADAPT is one of the largest prospective, randomized studies in early-stage breast cancer and was conducted by the West German Study Group (WSG) in 80 centers across Germany. It utilized a pioneering trial design to assess individualization of (neo)adjuvant decision-making.

"Our study shows the unique value of the complementary biological information provided by the Oncotype DX test and sequential Ki67 testing. Risk stratification using the Recurrence Score result and changes in Ki67 after brief pre-operative anti-hormonal therapy allows us to identify those patients with node-negative or node-positive disease who can be spared the toxicity and side effects of chemotherapy without a negative impact on treatment outcome," said Prof. Nadia Harbeck, Scientific Director of the WSG and Head of the Breast Centre at LMU Klinikum Munich (LMU), Germany. "This is especially important for patients who would be considered at high risk of relapse based on traditional clinical parameters."

New patient-specific meta-analysis provides individualized estimates for both prognosis and absolute chemotherapy benefit in node-negative breast cancer

A new patient-specific meta-analysis of data from more than 10,000 patients with node-negative disease assessed individualized estimates of distant recurrence risk and absolute chemotherapy benefit based on the integration of the Recurrence Score result with clinicopathologic features.[iii]This analysis builds on the practice-changing results from the TAILORx study, which prospectively defined the groups of patients who will and will not benefit from chemotherapy.

The meta-analysis was conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and was presented in an oral session at SABCS by lead author Joseph A. Sparano, M.D., associate director for clinical research at Albert Einstein Cancer Center and associate chair for clinical research in the department of oncology at Montefiore Health System in New York, and leader of the TAILORx study for the ECOG-ACRIN Cancer Research Group. The data was published concurrently in the December 2020 issue of the Journal of Clinical Oncology.

The patient-specific meta-analysis estimates will initially be made available to physicians in the United States, starting in December 2020, as an online educational tool called RSClin. The tool provides a more individualized prediction of absolute chemotherapy benefit that can enhance treatment decisions, particularly for patients whose Recurrence Score result is close to the TAILORx defined cut-off point of 25. By presenting the data in a new, easy-to-understand, visual format, RSClin empowers physicians with information that may be used to facilitate treatment conversations and decision-making with patients.

"As confirmed in TAILORx, for the great majority of patients, treatment based on the Recurrence Score result alone is clear," said Dr. Sparano. "The RSClin tool, which now incorporates data from TAILORx to reflect contemporary treatment outcomes, provides individualized estimates for both risk of distant recurrence and absolute chemotherapy benefit and continues to demonstrate the role of TAILORx in informing early-stage breast cancer treatment."

ECOG-ACRIN conducted the analysis primarily with funding from the National Cancer Institute. Mention of commercial products does not imply endorsement by the U.S. government. Additional support was provided by the Breast Cancer Research Foundation, the Komen Foundation, and the Breast Cancer Research Stamp issued by the United States Postal Service.

On December 11, 2020 PureTech Health plc (LSE: PRTC, Nasdaq: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported the initiation of its Phase 1 clinical trial of LYT-200 for the potential treatment of metastatic solid tumors that are difficult to treat and have poor survival rates (Press release, PureTech Health, DEC 11, 2020, View Source [SID1234572693]). LYT-200 is one of several novel therapeutic opportunities within PureTech’s Wholly Owned Pipeline that will be discussed today at its virtual R&D Day.

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"Each year, hundreds of thousands of people are diagnosed with solid tumors, and many will present with metastatic disease that do not respond to existing immunotherapy agents," said Zev Wainberg, M.D., co-director of the UCLA GI Oncology Program, associate professor of medicine at UCLA and the principal investigator on PureTech’s LYT-200 trial. "By targeting galectin-9, LYT-200 is designed to block foundational immunosuppressive mechanisms that shut down the body’s natural ability to fight a number of cancers. The unique mechanism of LYT-200 holds potential across a number of solid tumor types and may enable LYT-200 to be used as a single agent, as well as in combination with checkpoint inhibitors and other anti-cancer treatments."

LYT-200 is a clinical stage, fully human, monoclonal antibody (mAb), that is designed to target galectin-9, an immunosuppressive protein that simultaneously activates multiple immunosuppressive pathways in the tumor microenvironment and is prominently expressed in multiple difficult-to-treat cancers, including breast cancer, pancreatic and cholangiocarcinoma. It is currently being evaluated in the first stage of an adaptive Phase 1/2 trial. The primary objective of the Phase 1 portion of the trial is to assess the safety and tolerability of escalating doses of LYT-200 in order to identify a dose to carry forward into a subsequent Phase 2 trial. The Phase 1 will also assess LYT-200’s pharmacokinetic and pharmacodynamic profiles. Following the topline results, which are expected in the fourth quarter of 2021, PureTech intends to initiate the Phase 2 expansion cohort portion of the trial, which will further assess the recommended Phase 2 dose as a single agent or in combination with chemotherapy and anti-PD-1 therapy in multiple solid tumor types, including pancreatic cancer and cholangiocarcinoma.

"We are pleased to have initiated the Phase 1 part of our LYT-200 clinical trial, which is a dose-finding portion designed to assess safety and tolerability and explore preliminary signals of efficacy for LYT-200," said Aleksandra Filipovic, M.D. PhD, head of oncology at PureTech. "We have generated compelling preclinical data to date, which we believe support the potential of LYT-200 as a new anti-cancer therapy targeting galectin-9, both as a single agent and in combination with other anti-cancer therapies."

Dr. Zev Wainberg and Dr. Siddhartha Mukherjee, clinician and researcher at Columbia University and Pulitzer Prize-winning author of The Emperor of All Maladies and The Gene, will discuss their perspectives on the field of immuno-oncology during today’s virtual R&D Day, which will be available on the Investors section of the corporate website under Events & Presentations. To register, please sign up here.

About LYT-200

LYT-200 is a monoclonal antibody targeting a foundational immunosuppressive protein, galectin-9, for the potential treatment of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer and cholangiocarcinoma, that are difficult to treat and have poor survival rates. PureTech has presented preclinical data demonstrating high expression of galectin-9 across breast cancer, pancreatic and cholangiocarcinoma samples and found that the highest levels of galectin-9 correlated with shorter time to disease relapse and poor survival. These data suggest that galectin-9 could be significant both as a therapeutic target for a range of cancers and as a cancer biomarker. Preclinical animal and patient-derived organoid tumor models also showed the potential efficacy of LYT-200 and the importance of galectin-9 as a target. LYT-200 is currently being evaluated in a Phase 1/2 adaptive design trial, and results from the Phase 1 portion are expected in the fourth quarter of 2021.

About PureTech’s Virtual R&D Day

The virtual R&D Day will showcase PureTech’s scientific leadership in lymphatics and related immune pathways and detail PureTech’s Wholly Owned Pipeline. Product candidates within this pipeline include LYT-100, a clinical-stage, anti-fibrotic and anti-inflammatory small molecule being advanced for the potential treatment of interstitial lung diseases and lymphedema, LYT-200, a clinical-stage monoclonal antibody targeting foundational immunosuppressive mechanisms for the potential treatment of solid tumors, and LYT-300, an oral form of allopregnanolone that is being advanced into IND-enabling studies for a range of neurological conditions. Additionally, the R&D Day will detail PureTech’s discovery platforms, including the Glyph technology platform, which is designed to target therapeutics to the lymphatic system and potentially enabling oral administration of natural bioactive molecules such as neurosteroids and cannabinoids, and the Orasome technology platform, which is designed to enable the oral administration of biotherapeutics, such as antisense oligonucleotides, short interfering RNA, mRNA, modular expression systems for therapeutic proteins, peptides and nanoparticles.

On December 11, 2020 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 financial results for the third quarter ended September 30, 2020, as well as recent clinical progress (Press release, Akari Therapeutics, DEC 11, 2020, View Source [SID1234572660]).

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"With the imminent opening of our Phase III trial in pediatric patients with HSCT-TMA in Europe and a clear regulatory path in the U.S. and Europe for our Phase III study in patients with BP, we are now in the exciting position of progressing two Phase III programs in orphan diseases in which there are no approved treatments," said Clive Richardson, Chief Executive Officer of Akari Therapeutics.

Third Quarter 2020 and Recent Clinical Highlights

Akari’s two lead programs – in BP and HSCT-TMA – are in Phase III development. The Company also has programs addressing lung and ophthalmology diseases.

Phase III clinical trial in patients with BP

Akari expects to initiate a pivotal Phase III program for the treatment of BP in the first half of 2021, subject to the ongoing impact of COVID-19 related restrictions. Following positive FDA and EMA meetings the pivotal trial design is in two parts, with Part A and Part B having the same structure, duration, endpoints and target population of moderate and severe BP patients. This follows earlier positive data from Akari’s Phase II study of nomacopan in BP patients.
The EMA and the FDA have granted orphan drug designation for nomacopan for the treatment of BP.
Phase III clinical trial in pediatric patients with HSCT-TMA

Phase III study in pediatric HSCT-TMA is now opening for enrollment in Europe and we plan to open in the U.S. in the first quarter of 2021, subject to the ongoing impact of COVID-19 related restrictions.
Akari has both FDA fast track for pediatric HSCT-TMA patients and orphan drug designation status for this program.
Ophthalmology program

Interim data from the first-in-eye Phase I/II study in atopic keratoconjunctivitis (AKC), a surface of the eye inflammatory disease, showed that nomacopan was comfortable and well tolerated. Further, as previously disclosed, enrollment into Part B of this study was impacted by the COVID-19 pandemic. Akari has opened an investigational new drug application (IND) and is looking to expand its program into the broader surface of the eye market.
The Company’s back of the eye pre-clinical program is looking to build on the recent American Journal of Pathologypublication on uveitis. This result has potential implications for use of nomacopan in other back of the eye diseases such as AMD with the differentiating feature that nomacopan can potentially treat dry AMD which is associated with complement dysregulation while minimizing the risk of wet AMD due to nomacopan’s VEGF inhibitory effect of LTB4.
Given the specialist nature of the ophthalmology market, Akari is exploring opportunities to collaborate with potential partners to accelerate the development of these ophthalmology programs.
Lung program

In the UK, recruitment into the COVID-19 observational study is complete and an initial review of the study, which has been expanded from 50 to over 100 participants, is now expected early 2021. This observational study will provide data on complement and cytokine activity and the potential to optimize treatment with nomacopan by focusing on particular patient subgroups or time points in the disease.
In the U.S., the FDA has approved a randomized multi-center randomized study in patients hospitalized with COVID-19 pneumonia. Initiation of this study is expected in the first quarter of 2021. The clinical study in Brazil has been paused to optimize dosing due to a subset of patients whose complement levels did not remain fully ablated, indicating an unexpectedly high complement drive as recently reported by others (Prendecki et al 2020).
Akari is exploring opportunities to expand its lung program to include other inflammatory diseases with exacerbations, limited treatment options and where both complement and leukotriene pathways are implicated. In this context an investigator led severe asthma study is being considered in the US.
PNH – long term data

A separate press release issued today highlights new data from 19 PNH patients treated for over 30 cumulative patient-years showing that self-administered nomacopan is a well-tolerated and substantially reduces transfusion dependence.
Transfusion independence (defined as at least 6 months without transfusion) of 79% reported for 14 PNH patients treated with nomacopan for at least six months, who were transfusion dependent prior to treatment.
The long-term PNH data supports nomacopan’s therapeutic potential in other diseases where complement dysregulation plays a role, including Akari’s Phase III trials in BP and HSCT-TMA where both complement (C5) and leukotriene (LTB4) are implicated.
Third Quarter 2020 Financial Results

As of September 30, 2020, the Company had cash of approximately $12.3 million, compared to cash of $5.7 million as of December 31, 2019.
On June 30, 2020, the Company entered into a securities purchase agreement with Aspire Capital Fund, LLC (Aspire Capital) which provides that Aspire Capital is committed to purchase up to an aggregate of $30.0 million of the Company’s ADSs, with each ADS representing one hundred ordinary shares, during a 30-month term of the purchase agreement. As of September 30, 2020, the initial amount of $30.0 million remained available under the facility. Subsequent to the end of the third quarter in October 2020, the Company sold to Aspire Capital approximately $6.0 million of ordinary shares, which leaves $24 million of the original purchase commitment available under the facility.
Research and development (R&D) income in the third quarter of 2020 was approximately $1.6 million due to the receipt of $3.4 million in R&D tax credits. This compares to R&D expense of approximately $1.8 million in the same quarter the prior year.
General and administrative (G&A) expenses in the third quarter of 2020 were approximately $1.8 million, as compared to approximately $1.4 million in the same quarter last year. This increase was primarily due to higher expenses for legal fees and insurance.
Total other income for the third quarter of 2020 was approximately $1.7 million, as compared to total other income of $0.6 million in the same period the prior year. This change of $1.1 million was primarily due to approximately $1.0 million of gain related to the change in the fair value of the options and warrants liabilities in the third quarter of 2020 compared to the same period in 2019.
Net income for the third quarter of 2020 was approximately $1.4 million, compared to a net loss of approximately $2.6 million for the same period in 2019. The increase in net income was primarily due to higher total other income combined with R&D tax credits in 2020.
Important Message Regarding COVID-19

Akari’s clinical trial sites are based in areas currently affected by the global outbreak of the COVID-19 pandemic, and public health epidemics such as this can adversely impact the Company’s business as a result of disruptions, such as travel bans, quarantines, and interruptions to access the trial sites and supply chains, which could result in material delays and complications with respect to research and development programs and clinical trials. Moreover, as a result of the pandemic, there is a general unease of conducting unnecessary activities in medical centers. As a consequence, the Company’s ongoing trials have been halted or disrupted. For example, the Phase I/II clinical trial in patients with AKC study has been halted and recruitment in the Phase III clinical trial in pediatric patients with HSCT-TMA has been and may continue to be delayed. It is too early to assess the full impact of the coronavirus outbreak on trials for nomacopan, but coronavirus is expected to affect Akari’s ability to complete recruitment in the original timeframes. The extent to which the COVID-19 pandemic impacts operations will depend on future developments, which are highly uncertain and cannot be predicted with confidence, including the duration and continued severity of the outbreak, and the actions that may be required to contain the coronavirus or treat its impact. In particular, the continued spread of COVID-19 globally, could adversely impact the Company’s operations and workforce, including research and clinical trials and the ability to raise capital, could affect the operations of key governmental agencies, such as the FDA, which may delay the development of the Company’s product candidates and could result in the inability of suppliers to deliver components or raw materials on a timely basis or at all, each of which in turn could have an adverse impact on the Company’s business, financial condition and results of operation.