On April 28, 2021 Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, reported plans to release its financial results for the first quarter ended March 31, 2021, on Monday, May 10, 2021 before the opening of the financial markets (Press release, Akebia, APR 28, 2021, View Source [SID1234578678]).

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Akebia will host a conference call at 9:00 a.m. Eastern Time on Monday, May 10, to discuss its first quarter financial results and recent business highlights. To listen to the conference call, please dial (877) 458-0977 (domestic) or (484) 653-6724 (international) using conference ID number 6250159. The call will also be webcast LIVE and can be accessed via the Investors section of the Company’s website at View Source

A replay of the conference call will be available two hours after the completion of the call through May 16, 2021. To access the replay, dial (855) 859-2056 (domestic) or (404) 537-3406 (international) and reference conference ID number 6250159. An online archive of the conference call can be accessed via the Investors section of the Company’s website at View Source

On April 28, 2021 1 Redx Pharma (AIM: REDX), the drug discovery and development company focused on cancer and fibrosis, reported that it has successfully initiated dosing of the first patient cohort with a combination of RXC004, the Company’s lead drug candidate, and nivolumab (OPDIVO-Bristol Myers Squibb, an anti-PD-1 antibody) (Press release, Redx Pharma, APR 28, 2021, View Source [SID1234579170]). RXC004 is also currently being evaluated as monotherapy in a Phase 1 clinical study, from which top line results are expected by mid 2021.

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The primary objective of the Phase 1 combination study is to evaluate the safety and tolerability of RXC004 in combination with nivolumab in patients with advanced malignancies (ClinicalTrials.gov Identifier:NCT03447470). The announcement today confirms that the first three patients have initiated treatment with 1mg RXC004 along with nivolumab. The results from the combination study are expected to read out in H2 2021 and will be used to define a dose of RXC004 to be used in combination with standard dose nivolumab in a Phase 2 study in patients with genetically selected microsatellite stable (MSS) metastatic colorectal cancer (MSS mCRC), which is planned to start to recruit patients in H2 2021.

Lisa Anson, Chief Executive Officer of Redx Pharma said: "We are delighted to have initiated dosing of our first patient cohort in our Phase 1 RXC004 and anti-PD1 combination study. We believe that RXC004 has the potential to offer clinical benefit both as a monotherapy and in combination with immunotherapies for patients with Wnt-driven advanced solid tumours.

This important milestone opens our combination study programme, which is an exciting addition to our ongoing Phase 1 monotherapy study which is on track to report headline results by mid 2021"

What is RXC004?
RXC004 is a potent, selective, oral small molecule inhibitor of the enzyme, porcupine, a key activator of Wnt ligands in the Wnt signalling pathway. Aberrant Wnt signalling contributes directly to tumour growth and plays an important role in immune evasion, which leads to resistance to immune checkpoint inhibitors such as nivolumab. By selecting patients with tumours that have high Wnt ligand dependency, such as tumours with mutations in the RNF43 gene and fusions in the RSPO gene family, RXC004 has an opportunity to both directly inhibit the tumour growth and have an immune-enhancing effect to attack the tumour.

Why are we testing anti-PD1 and RXC004 in combination?
Immune checkpoint inhibitors (ICIs) such as anti-PD-1 antibodies have revolutionised the treatment of cancer, but do not work in all patients. Wnt pathway activation can enhance the ability of the tumour to evade destruction by the immune system and could contribute to lack of response to ICIs in these tumours. Our scientists have demonstrated preclinically that RXC004 can block activation of the Wnt pathway and restore the ability of the immune system to fight the tumour. Thus, RXC004 offers potential as a monotherapy or combination therapy, which we are now testing in clinical trials.

RXC004 Clinical trials
RXC004 is currently being investigated in a Phase 1 study, with top line safety and tolerability data as a monotherapy expected by mid 2021, with more detailed data expected to be presented at a conference in H2 2021. Following completion of the monotherapy Phase 1, clinical proof-of concept monotherapy studies in genetically-selected patients with metastatic colorectal cancer, genetically selected pancreatic cancer and all comers biliary cancer are expected to initiate. These studies are in addition to the combination study programme

On April 28, 2021 Isofol Medical AB (publ), (Nasdaq First North Premier Growth Market: ISOFOL), reported that the Board of Directors has the intention to carry out an issue of shares of approximately SEK 400 million with preferential rights for the Company’s existing shareholders (the "Rights Issue") (Press release, Isofol Medical, APR 28, 2021, View Source [SID1234578622]). An extraordinary general meeting will be held around May 14, 2021 (the "EGM") to propose to resolve to authorize the Board of Directors to resolve on the Rights Issue and the terms thereof. The EGM is also proposed to resolve to authorize the Board of Directors to resolve on a directed share issue, corresponding to approximately SEK 100 million, with deviation from the shareholders’ preferential rights (the "Over-Allotment Option"), in order to meet potential additional demand from strategic investors and thereby broaden the shareholder base. The notice to the EGM will be announced through a separate press release.

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Not for publication, distribution or release, directly or indirectly, in whole or in part, within or into the United Kingdom, US, Canada, Japan, Australia, Hong Kong, New Zeeland or any other jurisdiction in which such publication, distribution or release may be contravening to any applicable laws or rules. Additional restrictions are applicable, please see "Important information" in the end of this press release.

Summary
The Board of Directors announces its intention to propose an EGM to authorize the Board of Directors to carry out the Rights Issue and the potential Over-Allotment Option (provided that the Rights Issue is oversubscribed). The EGM scheduled to be held around May 14, 2021, will be announced through a separate press release.
The net proceeds from the Rights Issue and the potential Over-Allotment Option will be used to fund i) clinical development activities relating to the AGENT study beyond top-line results and activities for finalization of the NDA application, (ii) finalization of the development and validation of CMC, iii) global preparedness activities including the development of medical affairs and commercial launch packages, as well as continued partnering activities, iv) clinical development activities, including gene expression analysis and initiation of studies in additional indications and (v) general corporate purposes.
Subject to the EGM’s resolutions, the Rights Issue is fully guaranteed through subscription undertakings from current shareholders and guarantee commitments from current shareholders and external investors.
The potential Over-Allotment Option will be conditional upon the Rights Issue being oversubscribed.
Isofol’s CEO Ulf Jungnelius comments: "During the last year, Isofol has achieved several important milestones such as two partnership deals, a fully recruited AGENT study and in Q1 2021 a positive outcome of the interim analysis. Strengthening our financial position enables us to secure the financing needed to submit a New Drug Application to FDA and EMA, expected in H2 2022. Furthermore, it allows us to maintain a high pace in the pre-commercialization activities to ensure the prerequisites for a successful launch of arfolitixorin upon potential approval. We also see good potential to continue the development of gene expression analysis for arfolitixorin in order to bring new treatment options for cancer patients and to create value for our shareholders."

Background and intention
Isofol is a clinical stage biotech company developing arfolitixorin to improve the efficacy of standard of care chemotherapy for advanced colorectal cancer by increasing tumor response and progression free survival.

Arfolitixorin – the key active metabolite of widely used folate-based drugs – can potentially benefit more patients with advanced colorectal cancer as it does not require complicated metabolic activation to become effective. Arfolitixorin is currently being studied in the global Phase III AGENT study.

The 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 tumor cells. The study is designed to show superiority for arfolitixorin over leucovorin.

The AGENT study is fully recruited and is ongoing at approximately 90 sites in the U.S., Canada, Europe, Australia and Japan, where Isofol currently has 15 active sites.

Isofol raised approximately SEK 180 million in June 2020 through a rights issue and an over-allotment option. Since the June 2020 capital raise, Isofol has reached the mentioned and critical milestones for that capital raise, such as; the study is fully recruited, the interim result has been presented and the Company has signed licensing agreements with Solasia in Japan and Endo/Paladin in Canada. These licensing agreements are expected to positively affect Isofol’s financial position over time.

In March 2021 the independent Data Safety and Monitoring Board ("iDSMB") recommended continuation of the AGENT study with 440 patients, in accordance with the study design for arfolitixorin. The interim analysis was the fifth time the iDSMB has assessed safety data. Isofol views the iDSMB’s recommendation to continue the study without any amendments to the study protocols as an important signal that the treatment is safe. The treatment of enrolled patients will continue with follow-ups and repeated tumor measurements according to the study’s protocol. After 300 PFS events have taken place, either with tumor growth or that the patient has passed away, a data read out is initiated, with compilation and statistical analysis to present top line results. The Company expects these events to occur during the first and second halves of 2022.

The Board of Directors intends to carry out the Rights Issue and the potential Over-Allotment Option to ensure the continued and successful development of the Company, in accordance with its business plan and strategy. The intention of the Rights Issue and the potential Over-Allotment Option is primarily to fund i) clinical development activities relating to the AGENT study beyond top-line results and activities for finalization of the NDA application, (ii) finalization of the development and validation of CMC, iii) global preparedness activities including the development of medical affairs and commercial launch packages, as well as continued partnering activities, iv) clinical development activities, including gene expression analysis and initiation of studies in additional indications and (v) general corporate purposes.

Through the potential Over-Allotment Option, if exercised in full, the Company will receive an additional financing of approximately SEK 100 million before transaction costs. The potential Over-Allotment Option is conditional upon the Rights Issue being oversubscribed. The reason to deviate from the shareholders’ preferential rights is that the Board of Directors, in the event of strong interest from investors, wishes to further strengthen the Company’s capital as well as broaden the Company’s shareholder base with new strategic investors.

Subscription undertakings and guarantee commitments
The Rights Issue is fully guaranteed through subscription and guarantee commitments.

A number of investors have provided guarantee commitments, which together with subscription undertakings from several existing shareholders, including The Fourth Swedish National Pension Fund ("AP4"), in total represent SEK 400 million. In addition, certain shareholders including Handelsbanken Fonder and Swedbank Robur have expressed that they are supportive to the Rights Issue and that they intend to subscribe for their respective pro rata shares.

Members of the Board of Directors and Management, comprising Ulf Jungnelius, Pär-Ola Mannefred, Gustaf Albèrt and Anna Belfrage, who jointly hold approximately 0.4 percent of the Company’s outstanding shares have committed to subscribe their respective pro rata shares in the Rights Issue amounting to approximately SEK 1.8 million.

Shareholders representing in total approximately 12.3 percent of the shares and votes in the Company have undertaken to at the EGM vote to authorize the Board of Directors to carry out the Rights Issue and the potential Over-Allotment Option.

EGM and expected timetable for the Rights Issue
The Board of Directors convene the shareholders to the EGM through a separate press release. The EGM will take place around May 14, 2021. A detailed timetable and terms of the Rights Issue will be announced if the Board of Directors resolves on the Rights Issue.

Advisors
Carnegie Investment Bank AB (publ) and Pareto Securities AB act as Joint Bookrunners in connection with the Rights Issue and the potential Over-Allotment Option. Vinge law firm acts as legal adviser to Isofol, and Schjødt law firm acts as legal adviser to the Joint Bookrunners.

This is information that Isofol Medical AB (publ) 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 18:00 CEST on April 28, 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 Phase III study, AGENT. As the key active metabolite of the widely used folate-based drugs, arfolitixorin can potentially benefit more patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.

On April 28, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160) reported positive results from a planned interim analysis of the Phase 3 ALPINE trial comparing BRUKINSA (zanubrutinib) against ibrutinib in adults with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, BeiGene, APR 28, 2021, View Source [SID1234578640]).

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BRUKINSA met the primary endpoint of the trial, demonstrating non-inferiority in objective response rate (ORR) by both investigator and independent review committee (IRC) assessments (p < 0.0001). The trial also demonstrated superior ORR with a statistically significant improvement in ORR for BRUKINSA vs. ibrutinib (p = 0.0006) by investigator assessment, as well as a numerically higher ORR but not statistically significant improvement by IRC (p = 0.0121 compared to the two-sided stringent statistical boundary of p < 0.0099 set for the interim analysis). The interim analysis from this fully-enrolled, ongoing trial is based on 415 of 652 patients followed for a minimum of 12 months.

Data pertaining to progression-free survival (PFS) in the 652 patients, a secondary endpoint of the trial, were immature at the data cutoff for the interim analysis. However, the descriptive summaries of PFS showed an early trend favoring BRUKINSA.

The trial also met a pre-specified secondary endpoint related to safety. Compared to ibrutinib, BRUKINSA demonstrated a statistically significant lower risk of atrial fibrillation or flutter, which is characterized by an irregular heartbeat that can lead to blood clots, stroke, heart failure and other heart-related complications. Overall, the safety profile of BRUKINSA was consistent with the previously seen profile in its clinical development program.

ALPINE is BeiGene’s second Phase 3 head-to-head trial comparing BRUKINSA to ibrutinib.

Jane Huang, M.D., Chief Medical Officer, Hematology of BeiGene said, "The interim results from this head-to-head trial demonstrated that, as a selective inhibitor designed to deliver sustained and continuous inhibition of BTK, BRUKINSA provides CLL patients with improvements in response and reduced rates of atrial fibrillation or flutter compared to ibrutinib. Data from this interim analysis, in addition to BRUKINSA’s comprehensive clinical program, provide important new information to support its benefit-risk profile."

BeiGene plans to consult with global regulatory authorities on next steps and present these data at an upcoming major medical conference. ORR per IRC will be further assessed at the planned final analysis, and patients will be followed for analyses on key secondary endpoints including PFS.

About Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, with a global incidence of approximately 114,000 new cases in 2017.1,2 CLL affects white blood cells or lymphocytes in the bone marrow.1 Proliferation of cancer cells (leukemia) in the marrow result in reduced ability to fight infection and spread into the blood, which affects other parts of the body including the lymph nodes, liver and spleen.1,3 The BTK pathway is a known route that signals malignant B cells and contributes to the onset of CLL.4 Small lymphocytic lymphoma (SLL) is a non-Hodgkin’s lymphoma affecting the B-lymphocytes of the immune system, which shares many similarities to CLL but with cancer cells found mostly in lymph nodes.5

About ALPINE

ALPINE is a randomized, global Phase 3 trial (NCT03734016) comparing BRUKINSA against ibrutinib in previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

In the trial, a total of 652 patients were randomized into two arms with the first receiving BRUKINSA (160 mg orally twice daily) and the second receiving ibrutinib (420 mg orally once daily) until disease progression or unacceptable toxicity. The primary analysis of objective response rate (ORR), defined by pre-specified non-inferiority of BRUKINSA versus ibrutinib, was assessed by investigator and independent review committee (IRC) using the modified 2008 iwCLL guidelines with modification for treatment-related lymphocytosis for patients with CLL and per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. There was hierarchical testing of non-inferiority followed by superiority in ORR as assessed by investigator and IRC. Key secondary endpoints include progression-free survival (PFS), duration of response, overall survival, and incidence of adverse events. The study is ongoing, with pre-specified endpoints of ORR and PFS to be evaluated at the planned final analysis expected in 2022.

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.
BRUKINSA is approved in the following indications and regions:

•For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;

•For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;

•For the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;

•For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021); and

•For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021).

To-date, more than 30 marketing authorization applications in multiple indications have been submitted outside of the United States and China, covering the EU and more than 20 other countries.

*This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

**This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

On April 28, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that two trial in progress posters, on the Phase 1 INNATE clinical trial and the Phase 2 SELECT clinical trial, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting being held June 4-8, 2021 (Press release, Jounce Therapeutics, APR 28, 2021, View Source [SID1234578658]).

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Poster Details:

Poster Title: Phase 1, First-in-Human trial of JTX-8064, an anti-LILRB2/ILT4 monoclonal antibody, as monotherapy and in combination with anti-PD-1 in adult patients with advanced solid tumors (INNATE)
Presenter: Kyriakos P. Papadopoulos, MD, South Texas Accelerated Research Therapeutics (START), San Antonio, TX
Session Title: Developmental Therapeutics – Immunotherapy
Abstract Number: TPS2672
Date and Time: Friday, June 4, 2021; 9:00am ET

Poster Title: Phase 2 Study of PD-1 Inhibitor JTX-4014 (Pimivalimab) Alone and in Combination with Vopratelimab, an ICOS Agonist, in Biomarker-selected Subjects with Metastatic NSCLC After One Prior Platinum-containing Regimen (SELECT)
Presenter: Oleh Kobziev, MD, Regional Center of Oncology, Kharkiv, 61070, Ukraine
Session Title: Lung Cancer – Non-Small Cell Metastatic
Abstract Number: TPS9137
Date and Time: Friday, June 4, 2021; 9:00am ET

About JTX-8064

JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting and the 2019 and 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meetings support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical trial named INNATE (NCT04669899), of JTX-8064 as a monotherapy and in combination with either Jounce’s internal anti-PD-1 inhibitor, pimivalimab (formerly JTX-4014), or an approved anti-PD-1 inhibitor, is currently enrolling patients with advanced solid tumors.

About Pimivalimab

Pimivalimab (formerly JTX-4014) is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Pimivalimab demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, pimivalimab was shown to have an acceptable safety profile. Pimivalimab is currently being assessed in the INNATE Phase 1 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. Pimivalimab is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. The SELECT trial compares vopratelimab plus pimivalimab to pimivalimab alone in immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor.

About Vopratelimab

Vopratelimab is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab is currently being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with Jounce’s internal investigational PD-1 inhibitor, pimivalimab (formerly JTX-4014), compared to pimivalimab alone. The SELECT trial is currently enrolling approximately 75 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor. SELECT is powered to demonstrate the statistical superiority of the combination of vopratelimab plus pimivalimab compared to pimivalimab.