On August 22, 2020 Novartis reported that the Phase III COMBI-i study evaluating the investigational immunotherapy spartalizumab (PDR001), in combination with the targeted therapies Tafinlar (dabrafenib) and Mekinist (trametinib), did not meet its primary endpoint of investigator-assessed progression-free survival (Press release, Novartis, AUG 22, 2020, View Source [SID1234563952]). The trial was conducted among untreated patients with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600 mutation-positive cutaneous melanoma, compared to Tafinlar + Mekinist alone3.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"While the COMBI-i trial did not reach its primary endpoint, the study’s findings give us valuable insights into the role the investigational immunotherapy spartalizumab may play in future cancer therapy combinations and underscore the previously established importance of Tafinlar + Mekinist for these patients," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "Novartis remains committed to melanoma patients through ongoing research, and we continue to deliver the approved combination therapy Tafinlar + Mekinist to patients around the world. We extend our gratitude to the patients and investigators who participated in the COMBI-i study. Their partnership has expanded our understanding of spartalizumab and its potential role in future cancer treatments."

Novartis and the COMBI-i study investigators will continue to review the data to learn more from the results, which are expected to be submitted for presentation at a future medical meeting. Novartis remains committed to exploring new uses for immunotherapy in cancer treatment, including the ongoing development of spartalizumab, across a range of tumor types.

About the COMBI-i Study3
COMBI-i was a randomized, double-blind, placebo-controlled, Phase III study comparing the combination of anti-PD1 spartalizumab with Tafinlar (dabrafenib) and Mekinist (trametinib) versus the combination of placebo with Tafinlar and Mekinist. The study was conducted among previously untreated patients with unresectable or metastatic BRAF V600 mutation-positive melanoma. The COMBI-i study was conducted in three parts. Results reported today are from part 3 of the trial.

About Spartalizumab (PDR001)
Spartalizumab is an investigational monoclonal antibody directed against the human programmed death-1 (PD-1) receptor. Its development program continues investigating the immunotherapy across a range of tumor types.

About Tafinlar + Mekinist Combination
Tafinlar and Mekinist are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:

That has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
That has a certain type of abnormal "BRAF" (V600E or V600K mutation-positive) gene
Tafinlar and Mekinist are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal "BRAF" gene from coming back after the cancer has been removed by surgery.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal "BRAF V600E" gene.

Tafinlar and Mekinist are prescription medications that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):

That has spread to other parts of the body and you have no satisfactory treatment options, and
That has a certain type of abnormal "BRAF" gene
Tafinlar, in combination with Mekinist, should not be used to treat people with wild-type BRAF melanoma. Mekinist should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.

Your health care provider will perform a test to make sure that Tafinlar and Mekinist , in combination, are right for you.

It is not known if Tafinlar and Mekinist are safe and effective in children.

Tafinlar and Mekinist, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.

When Tafinlar is used in combination with Mekinist, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feel weak, cough up blood or blood clots, vomit blood or their vomit looks like "coffee grounds," or red or black stools that look like tar.

Mekinist, alone or in combination with Tafinlar, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider immediately if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.

Tafinlar, in combination with Mekinist, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.

The combination of Tafinlar and Mekinist can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.

Tafinlar, in combination with Mekinist, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.

Tafinlar, in combination with Mekinist, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.

Fever is common during treatment with Tafinlar in combination with Mekinist, but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.

Rash and other skin reactions are common side effects of Tafinlar in combination with Mekinist. In some cases, these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.

Some people may develop high blood sugar or worsening diabetes during treatment with Tafinlar in combination with Mekinist. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.

Tafinlar may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.

Tafinlar, in combination with Mekinist, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.

Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with Tafinlar and Mekinist and for at least 4 months after the last dose of Tafinlar and Mekinist. For women of reproductive potential, Tafinlar and Mekinist, in combination, may harm your unborn baby. Use effective birth control (contraception) during treatment with Tafinlar and Mekinist in combination, and for 4 months after stopping treatment with Tafinlar and Mekinist. The most common side effects for patients with metastatic melanoma are: pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma receiving the combination as adjuvant therapy are: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.

On August 21, 2020 Ono Pharmaceutical Co., Ltd. reported that ONO received a supplemental approval for Velexbru (generic name: tirabrutinib hydrochloride) Tablet 80mg ("Velexbru"), a Bruton’s tyrosine kinase ("BTK") inhibitor, in Japan for additional indication of Waldenstrom macroglobulinemia and lymphoplasmacytic lymphoma, for a partial change in approved items of the manufacturing and marketing approval (Press release, Ono, AUG 21, 2020, View Source [SID1234584587]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This approval is based on the result from a multi-center, open-label, single-arm Phase II study (ONO4059-05), evaluating Velexbru in patients with previously untreated, or relapsed or refractory Waldenstrom macroglobulinemia (WM) and lymphoplasmacytic lymphoma (LPL). In 27 patients who received tirabrutinib (untreated 18 patients and relapsed or refractory 9 patients) in this study, the overall response rate (partial response or greater) assessed by an independent review committee (IRC), a primary endpoint, was 88.9% (16/18 patients) (95% CI: 65.3 – 98.6) in the untreated group, and 88.9% (8/9 patients) (95% CI: 51.8 – 99.7) in the relapsed/refractory group. The secondary endpoints of progression-free survival (PFS) and overall survival (OS) were 100% at 6 months both in the untreated group and relapsed/refractory group. The most commonly observed grade ≥3 adverse events (AEs) were neutropenia and lymphopenia (11.1% each), and leukopenia (7.4%).

With this approval, Velexbru becomes the first BTK inhibitor approved for the treatment of patients with previously untreated, relapsed or refractory WM and LPL in Japan. Velexbru was designated as an orphan drug for the indication of WM and LPL by the Ministry of Health, Labour and Welfare (MHLW) in Japan on November 19, 2019.

About Waldenstrom macroglobulinemia ("WM") and lymphoplasmacytic lymphoma ("LPL") WM and LPL are one of the malignant lymphomas and are classified as "indolent lymphoma" which means one with relatively slow progression*1. It is estimated that there are approximately 240 new cases* 2,3 with LPL per year in Japan. WM and LPL generally grow and spread slowly in the clinical course, with a median survival of more than 5 years, but these are intractable diseases that cannot be cured with existing therapies*4. In Japan, standard treatment has not been established in patients with untreated relapsed or refractory WM and LPL, so a new treatment option is expected for these patient populations.

About ONO-4059-05 Study This study is a multi-center, open-label, single-arm Phase II study, evaluating the efficacy and safety of a monotherapy with Velexbru in patients with previously untreated, or relapsed or refractory WM and LPL. In this study, 27 patients were recruited (untreated 18 patients and relapsed or refractory 9 patients). Patients received Velexbru 480 mg (fasted) once daily and were treated until disease progression or unacceptable toxicity. The primary endpoint of this study is the overall response rate (partial response or greater) assessed by an independent review committee (IRC). The secondary endpoints are progression-free survival (PFS) and overall survival (OS).

About Velexbru Velexbru (tirabrutinib hydrochloride), discovered and developed by ONO, is a highly selective, oral BTK inhibitor and has been developed for the treatment in patients with B-cell tumors and autoimmune diseases in Japan. B cell receptor ("BCR") signaling plays a core role in the survival, activation, proliferation, maturation and differentiation of B cell lymphocyte. The BCR signaling pathway is known to be permanently activated, particularly B cell non-Hodgkin lymphoma (B-NHL) and chronic lymphocytic leukemia (CLL). Velexbru is expected to have a therapeutic effect because it inhibits BTK, a mediator located downstream of BCR. In December 2014, ONO out-licensed Tirabrutinib to Gilead Sciences, Inc. (Gilead) to allow Gilead the right to develop and commercialize the product in all countries of the world, except Japan, South Korea, Taiwan, China and ASEAN countries where ONO retains the development and commercialization rights of the product. In Japan, Velexbru was approved in March 2020 and launched in May 2020 for the treatment of relapsed or refractory primary central nervous system lymphoma (PCNSL).

On August 21, 2020 Affibody Medical AB (publ) ("Affibody" or "the Company"), a Swedish biotechcompany focused on developing next generation biopharmaceuticals based on its unique proprietary technology platforms: Affibody molecules and Albumod, reported its Second Quarter Report for 2020 (Press release, Affibody, AUG 21, 2020, View Source [SID1234575697]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Financial Highlights

Revenue for the 2nd Quarter 2020 amounted to SEK 109.6 (217.0) m, and to 119.2 (247.0) m for the full six-month period
Operating result for the quarter amounted to SEK 9.5 (153.2) m, and to -48.6 (128.3) m for the full six-month period
Net result for the quarter amounted to SEK 8.1 (147.6) m, and to -50.9 (122.9) m for the full six-month period
Cash flow for the quarter amounted to SEK -18.9 (315.5) m, and to -97.2 (326.1) m for the full six-month period
Cash and cash equivalents at the end of the period amounted to SEK 277.5 (417.1) m
Significant Events during period

On April 30, 2020 we announced that Daewoong, a South Korea-based pharmaceutical company, had exercised an option under the collaboration related to a half-life extended biotherapeutics product
On May 15, 2020, we and Inmagene Biopharmaceuticals announced a strategic partnership to develop and commercialize ABY-035, a bispecific molecule targeting Interleukin-17A (IL-17), for multiple auto-immune diseases. Inmagene will be responsible for commercialization in mainland China, Hong Kong, Taiwan, and Macau (Greater China), and South Korea, as well as development activities in the Asia Pacific region, excluding Japan. Affibody will retain global commercial rights outside of Greater China and South Korea. The partners will work together to enroll patients into global registrational trials to support Biologics License Applications (BLAs) in multiple indications worldwide. Under the terms of the agreement, Affibody will receive a $10 million upfront payment and is eligible to receive up to $215.5 million in additional regulatory and sales milestones, plus royalties on sales in Inmagene’s commercialization territory.
On June 15, 2020 we announced positive top-line data from our Phase 2, 52-week trial investigating the novel bispecific IL-17A inhibitor ABY-035 in patients with moderate-to-severe psoriasis ("AFFIRM-35").
On June 15, 2020 we announced the completion of the ABY-039 Phase 1 trial and the termination of the ABY-039 program, our FcRn inhibitor, due to tolerability observations that would limit the target product profile of subcutaneous high dose once monthly maintentance injections. Based on these observations Alexion has terminated the co-development agreement with Affibody.
Significant Events during the rest of the Year

An EGM on February 17, 2020 elected José Suarez as Board member.
Affibody is a clinical stage biopharmaceutical company with a broad product pipeline focused on developing innovative bi- and multi-specific next generation biopharmaceuticals based on its unique proprietary technology platforms: Affibody molecules and Albumod.

The company operates a focused experimental medicine model and currently has two clinical stage programs. The first is a therapeutic program that targets psoriasis. The second program is a diagnostic imaging program that is directed primarily towards metastatic breast cancer.

Affibody AB is a holding of Patricia Industries.

On August 21, 2020 Tiziana Life Sciences plc (Nasdaq: TLSA; AIM: TILS) ("Tiziana" or the "Company"), a biotechnology company focused on innovative therapeutics for oncology, inflammation and infectious diseases, reported that the United States Patent and Trademark Office ("USPTO") has granted a patent on use of Milciclib in combination with tyrosine kinase inhibitors (TKIs) such as Sorafenib (Nexavar), Regorafenib (Stivarga) and Lenvatinib (Lenvima) for the treatment of hepatocellular carcinoma (HCC) and other cancers in humans (Press release, Tiziana Life Sciences, AUG 21, 2020, View Source [SID1234568595]). This patent will be published by the USPTO on 1 September 2020 as Patent No. 10,758,541 (Inventor: Kunwar Shailubhai). Like most human cancers, HCC is a complex multi-factorial cancer with multiple underlying mechanisms causing enormous heterogeneity in patient populations. Consequently, patients with HCC often develop resistance towards the monotherapies of existing therapeutics. Thus, there is an urgent need for combination drug treatment approaches targeting different mechanisms to achieve better clinical outcomes.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Recently, the Company presented two posters on clinical evaluation of Milciclib at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 (ASCO2020). The poster on Phase 2a clinical evaluation of Milciclib, a broad-spectrum inhibitor of cyclin dependent kinases, indicated that the treatment was well-tolerated, and it produced encouraging clinical activity in sorafenib-resistant patients of HCC(1). The second poster was on the evaluation of Milciclib in combination with Regorafenib, a specific TKI drug, in liver transplant patients with HCC recurrence in the MiHRCO (Milciclib and Half Regorafenib CO administration) trial. The combination treatment was safe and produced promising clinical response(2) in these delicate and difficult to treat patients. Additionally, the Company earlier reported data from an animal study suggesting that the combination of Milciclib with Sorafenib, both acting via different mechanisms, suppressed expression of protooncogene c-Myc to produce pronounced synergistic anti-HCC activity(3).

Dr. Kunwar Shailubhai, CEO & CSO of Tiziana Lifesciences, commented, "Advanced cases of patients with HCC have limited therapeutic options because of the heterogeneity of the multiple mechanisms underlying the development of drug resistance and limited clinical responses. Thus, combination of drugs with different mechanism of actions are necessary to achieve superior clinical outcome. We are delighted that we now have this key patent on use of Milciclib in combination with other HCC drugs, including a TKI. Issuance of this patent strengthens our clinical strategy as we move forward with the combination of Milciclib and a TKI for the clinical evaluation of advanced cases of HCC as well as in patients with recurrent HCC after liver transplantation."

The person who arranged for the release of this announcement was Dr Kunwar Shailubhai, Chief Executive Officer and Chief Scientific Officer of the Company

Cited References:

1. Villa, E., Piscaglia, F., Geva, R., Dalecos, G., Papatheodoridis, G., Ciomei, M., Davite, C., Crivori, P., Palejwala, V., Jacob, J., Hamzeh, F., Shailubhai, K., Santoro, A., and A., S. (2020) Phase 2a Safety and Efficacy of Milciclib, a Pan-Cyclin Dependent Kinase Inhibitor, in Unresectable, Sorafenib-Refractory or -Intolerant Hepatocellular Carcinoma Patients. ASCO (Free ASCO Whitepaper) Abstract #29856

2. Pivetti, A., Di Marco, L., Bristot, L., Milosa, F., Maria Critelli, R., De Maria, N., Di Benedetto, F., Palejwala, V., Jacob, J., Shailubhai, K., and Villa, E. (2020) Safety and Clinical Activity of Combination Treatment with Regorafenib and Milciclib in Liver Transplant Patients with Hepatocellular Carcinoma Recurrence. ASCO (Free ASCO Whitepaper) Abstract #307309

3. Jindal, A., Palejwala, V. a., and Shailubhai, K. (2018) Oral Treatment with Milciclib Either Alone or in Combination with Sorafenib Inhibited Tumor Growth in an Orthotopic Model of Hepatocellular Carcinoma. Hepatology 68, 879A

About Milciclib (TZLS-201)

Milciclib (PHA-848125AC) is a small molecule inhibitor of several cyclin dependent kinases such as CDK1, CDK2, CDK4, CDK5 and CDK7. CDKs are serine threonine kinases that play crucial roles in progression of the cell cycle from G1 to S phase. Overexpression of CDKs and other downstream signaling pathways that regulate cell cycles have been frequently found to be associated with development of resistance towards chemotherapies. In a phase I study, oral treatment with Milciclib was found to be well-tolerated and the drug showed promising clinical responses in patients with advanced solid malignancies such as in NSCLC, pancreatic and colon cancer, thymic carcinoma and thymoma.

On August 21, 2020 Prescient reported that it is focused on developing novel, personalised therapies against a range of cancers (Press release, Prescient Therapeutics, AUG 21, 2020, View Source;utm_medium=rss&utm_campaign=health-kick-podcast-chemos-diminishing-role-the-personalised-approach-to-cancer-treatment-and-ptxs-car-t-innovations [SID1234567639]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The company’s universal CAR-T and targeted therapies are both personalised medicine approaches that seek to improve patient outcomes and provide new tools for clinicians in combating cancer.

Prescient has a broad pipeline of personalised cancer treatments, comprising CAR-T and targeted therapies, and spanning a range of different cancers.

The company made headlines earlier this month with news of its partnership with global cancer heavyweight Peter MacCallum Cancer Centre to develop new treatments.