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5 new targets for immune oncology in 2019

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Immune oncology (IO) is the focus of current drug development. In recent years, the development of many IO drugs around the world has been rapidly improving not only in speed but also in quality, which brings new hope to almost all types of cancer patients, including many rare cancer types. At present, IO therapy targeting PD- (L) 1 has achieved great clinical success, and has attracted more and more research teams.

Many agencies have predicted that in the next few years, the size of the global IO market will continue to grow rapidly. According to GrandView Research, the size of the IO market in 2018 was $ 58.1 billion, and it is expected to reach $ 126.9 billion in 2026. Transparency Market Research and Market Research Engine predict that the IO market will reach 124.88 billion US dollars and 173 billion US dollars in 2024, respectively. These optimistic predictions showed a significant increase in clinical activity, with the expected launch of many new treatments for IO.

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Last year, Incyte and Merck Epacadostat / Keytruda encountered huge failure in the clinical phase III of melanoma. This hit the development of epacadostat and other IDO inhibitors. At the same time, it also reduced the industry's enthusiasm for development of cancer immunotherapy.

However, research on novel immune checkpoint targets that stop tumor cells from fighting the immune response or stimulate the body's immune system against cancer is continuing. A recent statistics from the American Cancer Institute (CRI) found that more than 1,700 joint studies involving PD- (L) 1 inhibitors are currently underway.

Early and mid-term research data on these novel immune checkpoint targets may be seen at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

  1. 1.Target: STING (interferon gene complex stimulant)

Type: Immune stimulation

Related companies: Aduro and Novartis' ADU-S100, GlaxoSmithKline's GSK3745417, Merck MK-1454

Aduro and Merck's STING pathway candidate drugs are administered by intratumoral injection, meaning they can be used for melanoma, but may not have much applicability for cancers deep in the body. The MK-1454 data released at the 2018 European Society of Oncology Medical Association showed that the efficacy of combination with Keytruda was not obvious. GSK3745417 from GlaxoSmithKline (GSK) can be administered by intravenous infusion, and early drug trials are currently underway. Data from the combined use of ADU-S100 and Novartis anti-PD-1 therapy spartalizumab will be presented at this year's ASCO Annual Meeting.

  1. 2.Target: LAG-3 (lymphocyte activating gene-3)

Type: Immunosuppression

Related companies: GSK TSR-033, Regenerative REGN 3767; Bristol-Myers Squibb BMS-986016, F-Star Corporation FS118

TSR-033 is one of GSK's $ 5.1 billion acquisition of Tesaro's oncology assets. The clinical progress of the drug has received much attention. Regeneron and BMS will also show the latest progress of their drug candidates and their respective PD-1 inhibitors at the ASCO Annual Meeting. F-Star's FS118 is a bispecific antibody that targets both PD-1 and LAG-3. The drug has signed an option agreement with Merck, but recently Merck abandoned its option and F-Star re- Obtained full development rights for the drug.

  1. 3.Target: TIM-3 (T cell immunoglobulin and mucin domain-3)

Type: Immunosuppression

Related companies: Eli Lilly LY3321367, BeiGene BGB-A425, Symphogen SYM023, Novartis MBG453

This class of drugs is a classic match with PD- (L) 1. All of the above drugs are in Phase I clinical trials, in combination with experimental PD- (L) 1 drugs from each company and with externally approved immune checkpoint inhibitors. Early safety data provided by Eli Lilly showed high levels of anti-drug antibody response (without affecting pharmacokinetics) and evidence of tumor response. At present, no other data on this class of drugs has been released.

  1. 4.Target: TGFβ

Type: Immunosuppression

Related companies: Merck and GSK's bintrafusp alfa (bispecific PD-L1), Forbius Avid200, Lilly Galunisertib, University of Pennsylvania CART-PSMA-TGFβRd.

Of all the oncology challenges, the biggest bet may be Merck's decision to confront Merck in frontline non-small cell lung cancer. The hypothesis of this study is that bispecific bintrafusp alfa can block the PD-1 pathway as effectively as Keytruda, while inhibiting TGF-β provides additional benefits by blocking another mechanism that tumors use to shut down the immune response. Meanwhile, Eli Lilly has been evaluating galunisertib for the past few years and has reported some promising phase II data for pancreatic cancer. TGFβ also appears to be the only novel immune checkpoint target on the list considered a potential therapeutic technology, and the University of Pennsylvania is currently testing metastatic castration resistance to prostate cancer.

  1. 5.Targets: OX40

Type: Immune stimulation

Related companies: Pfizer PF-04518600, Bristol-Myers Squibb BMS986178, Incygn IncAGN1949

These drug candidates are in very early human clinical trials testing dose levels and biological responses. BMS research combined BMS986178 with Opdivo and Yervoy and found that BMS986178 stimulated the immune response. Pfizer's PF-04518600 has achieved disease stabilization in some patients.

Creative Bioarray possesses a research team, which has been focused on Immune-Oncology for decades. Since there are still lots of incomplete scientific understanding of tumor immunology, which gives rise to little widespread use of I-O therapies in clinic, Creative Bioarray is always ready to help and cooperate with customers on their I-O research or preclinical experiment. With multitudinous tumor cells, diverse animal tumor models, and various tumor research related services, such as cell cycle assaysapoptosis assaysproliferation assays, migration assays and toxicology assays, Creative Bioarray could offer professional design and experiment for customers to facilitate their I-O program.


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