$OTLC in immunotherapy space:
Immunotherapy (Checkpoint Inhibitors, CAR-T, IL-2, Vaccine)
The concept of immunotherapy is the mobilization of a patient’s immune system to fight cancer. As malignant cells arise in the body, they accumulate mutations leading to neoantigens that activates immune system to clear them. However, at the same time, cancer cells develop multiple resistance mechanisms to evade immune recognition and destruction. The most important immunosuppressive mediators is transforming growth factor-beta (TGF-β).
Immune checkpoint inhibitors (ICIs) are currently at the forefront of cancer therapy, as they display successful long lasting antitumor efficacy. However, only 15% of patients respond to immunotherapy. TGFβ drives immune response evasion and attenuate the tumor response to anti-PD-L1 therapy.
In fact, an open-label, multi-center study assessed the safety, tolerability, pharmacokinetics and antitumor activity of Vactosertib- a TGFβ inhibitor- in combination with Pembrolizumab (Keytruda, Merck) in patients with either metastatic colorectal or gastric cancer or gastroesophageal junction adenocarcinoma yielded promising efficacy data.
CAR T cell therapy has demonstrated remarkable success by utilizing engineered T cells with tumor antigens that lead to the recognition and attack of tumor cells in blood cancers; however, this method still remains a big challenge for treating solid tumors partially due to TGFβ-mediated immunosuppression. Inhibiting TGFβ signaling in CART cells can boost their antitumor efficacy in solid tumors.
Overcoming CART cell repression by interfering with TGFβ signaling have yielded promising results among multiple clinical trials.
Because of these insights into TGFβ’s immunosuppressive function, the combination of anti- TGFβ therapy and immunotherapy is under intensive investigation.
Recent large deals around TGFβ
Bristol Myers Squibb Enters Agreement to Acquire Forbius, Adding Lead TGF-beta Asset to Portfolio. 08/24/2020
Merck acquires Tilos, a biopharmaceutical developer targeting the latent TGF-beta complex for the treatment of cancer, fibrosis, and autoimmune diseases for $773M. 06/11/2019
GSK to co-develop Merck KGaA’s cancer immunotherapy candidate M7824 in 4.2B alliance. Feb 5, 2019. GlaxoSmithKline paid Merck KGaA €300 million ($355 million) upfront to jointly develop M7824, a bifunctional fusion protein immunotherapy that targets TGF-beta and PD-L1.
Pfizer moved TGF-beta 1 inhibitor PF-06952229 into the clinic in advanced solid tumor patients in 2018.
Scholar Rock began evaluating its prospect SRK-181 in combination with a checkpoint inhibitor in solid tumor patients this year.
https://www.fiercebiotech.com/biotech/bristol...cing-drugs
OT-101 as TGFβ drug candidate
OT-101 as the only late stage anti-TGFβ drug has the potential of transforming immunotherapy making checkpoint inhibitors and CAR-T more effective. Given the current appetite from Merck for TGFβ inhibitor, it should not be surprising that they are looking at combining OT-101 with their PD-1 inhibitor- Keytruda. If successful this could be the game changer for immunotherapy and propel Keytruda to >10B in revenue. The announcement OTLC did this morning essentially spelled out this scenario and bode well for company share price.
Immunotherapy (Checkpoint Inhibitors, CAR-T, IL-2, Vaccine)
The concept of immunotherapy is the mobilization of a patient’s immune system to fight cancer. As malignant cells arise in the body, they accumulate mutations leading to neoantigens that activates immune system to clear them. However, at the same time, cancer cells develop multiple resistance mechanisms to evade immune recognition and destruction. The most important immunosuppressive mediators is transforming growth factor-beta (TGF-β).
Immune checkpoint inhibitors (ICIs) are currently at the forefront of cancer therapy, as they display successful long lasting antitumor efficacy. However, only 15% of patients respond to immunotherapy. TGFβ drives immune response evasion and attenuate the tumor response to anti-PD-L1 therapy.
In fact, an open-label, multi-center study assessed the safety, tolerability, pharmacokinetics and antitumor activity of Vactosertib- a TGFβ inhibitor- in combination with Pembrolizumab (Keytruda, Merck) in patients with either metastatic colorectal or gastric cancer or gastroesophageal junction adenocarcinoma yielded promising efficacy data.
CAR T cell therapy has demonstrated remarkable success by utilizing engineered T cells with tumor antigens that lead to the recognition and attack of tumor cells in blood cancers; however, this method still remains a big challenge for treating solid tumors partially due to TGFβ-mediated immunosuppression. Inhibiting TGFβ signaling in CART cells can boost their antitumor efficacy in solid tumors.
Overcoming CART cell repression by interfering with TGFβ signaling have yielded promising results among multiple clinical trials.
Because of these insights into TGFβ’s immunosuppressive function, the combination of anti- TGFβ therapy and immunotherapy is under intensive investigation.
Recent large deals around TGFβ
Bristol Myers Squibb Enters Agreement to Acquire Forbius, Adding Lead TGF-beta Asset to Portfolio. 08/24/2020
Merck acquires Tilos, a biopharmaceutical developer targeting the latent TGF-beta complex for the treatment of cancer, fibrosis, and autoimmune diseases for $773M. 06/11/2019
GSK to co-develop Merck KGaA’s cancer immunotherapy candidate M7824 in 4.2B alliance. Feb 5, 2019. GlaxoSmithKline paid Merck KGaA €300 million ($355 million) upfront to jointly develop M7824, a bifunctional fusion protein immunotherapy that targets TGF-beta and PD-L1.
Pfizer moved TGF-beta 1 inhibitor PF-06952229 into the clinic in advanced solid tumor patients in 2018.
Scholar Rock began evaluating its prospect SRK-181 in combination with a checkpoint inhibitor in solid tumor patients this year.
https://www.fiercebiotech.com/biotech/bristol...cing-drugs
OT-101 as TGFβ drug candidate
OT-101 as the only late stage anti-TGFβ drug has the potential of transforming immunotherapy making checkpoint inhibitors and CAR-T more effective. Given the current appetite from Merck for TGFβ inhibitor, it should not be surprising that they are looking at combining OT-101 with their PD-1 inhibitor- Keytruda. If successful this could be the game changer for immunotherapy and propel Keytruda to >10B in revenue. The announcement OTLC did this morning essentially spelled out this scenario and bode well for company share price.
