It’s no secret that discovering and developing cancer drugs is an expensive and risky endeavor. But Cullinan Oncology is betting that a financial approach, rather than a purely scientific one, can improve the odds, and it has raised $150 million to test its approach.

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The Series A investment for Cambridge, MA-based Cullinan was co-led by the UBS Oncology Impact Fund and F2 Ventures. The UBS Oncology Fund is managed by Cambridge venture capital firm MPM Capital.

Investors want to put their money into healthcare, and into cancer drugs in particular, says Cullinan CEO Owen Hughes, who is also a managing director at MPM. But many cancer drug companies are focused on a single compound. This "binary situation," where a company’s fortunes are linked to the success or failure of one drug, makes for a very risky investment, Hughes says.

Just as a real estate investor might bet on a range of properties, Cullinan aims to spread investor risk across several drug candidates. The company will develop its portfolio from external sources, Hughes says. Internally, Cullinan will work on concepts and modeling of next-generation cancer treatments.

The goal is to end a drug program quickly if the early research suggests it won’t work. Hughes contends that under Cullinan’s model, killing off one or two compounds won’t diminish the value of the company.

"If we don’t get the results we like, we will shut it down and move on to other projects in the portfolio," Hughes says.

The Cullinan portfolio will have anywhere from eight to 12 drugs at any given time. Each drug will have a dedicated chief executive. But Cullinan won’t build large teams around each drug. Instead, the programs—whether they come from within Cullinan or are licensed from outside the company—will share resources within Cullinan and also outsource work to contract research organizations, both of which are cash-conserving measures. Hughes says that while Cullinan has the intellectual and scientific capacity to create new molecules, the company is choosing a different approach that the company hopes gets to a decision point more quickly, and at less cost, compared to traditional drug companies.

The idea of collecting drug assets and having them share resources is catching on in biotech investing. Last month, Palo Alto, CA-based BridgeBio Pharma raised $135 million for its "hub and spoke" model that splits each drug into a subsidiary that shares in the central resources of the parent. Boston-based biotech accelerator Xontogeny also aims to offer its portfolio companies the opportunity to share resources in certain areas, such as regulatory affairs.

Cullinan’s scientific work is led by co-founder and chief scientific officer Patrick Baeuerle, who is also a managing director at MPM. Baeuerle has co-founded oncology startups in the firm’s portfolio including TCR2 Therapeutics in Cambridge, South San Francisco, CA-based Harpoon Therapeutics, and Maverick Therapeutics, a Brisbane, CA, company. Cullinan has three compounds in its pipeline so far; Baeuerle would only describe them only in general terms. The company’s lead drug goes after a "well-known cancer target" that is, or was, considered undruggable, he says. This compound, which Baeuerle says was initially developed at a U.S. university, has potential applications in many cancers and is expected to start clinical trials in 15 to 18 months.

The other two Cullinan programs are internally developed immune-oncology treatments: one is a way of stimulating the immune system to fight cancer and the other is a type of cancer vaccine that Baeuerle says goes after a target that has not been addressed before.

The external candidates that Cullinan brings into its pipeline could come from universities or drug companies, though Baeuerle adds that compounds from companies tend to be further along in development. Cullinan is mainly looking for compounds that have yet to reach clinical trials or are in Phase 1 testing. At the rate that Cullinan is finding external innovations in cancer research, Baeuerle says the company’s pipeline might end up weighted toward external drug candidates.

"We’re agnostic where it comes from as long as it’s great science, as long as it has great promise to become a drug," Baeuerle says.

Hughes says that how much the company spends on each drug candidate will vary from drug to drug. The goal is to advance a drug far enough along to show how it could work, then license it, sell it, or perhaps spin it off into a separate company that goes public. The full $150 million of the Series A round is available now to Cullinan, though Hughes says the company won’t spend it all at once. But he adds that as Cullinan make progress, the company could raise even more money in the future.

Photo by Cullinan Oncology.

On October 3, 2017 Kancera reported that the company’s ROR inhibitor KAN0441571 effectively eliminates ROR1-bearing leukemic cells in a mouse model of human chronic lymphocytic leukemia (Press release, Kancera, OCT 3, 2017, View Source;releaseID=1373958 [SID1234520782]).

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The study was conducted in mice into which leukemia cells from a patient with chronic lymphocytic leukemia were introduced. Human leukemia cells were allowed to infiltrate the lymphatic system in mice for one week, as also occurs in humans. Thereafter treatment began, consisting of two doses of KAN0441571 given every 3 days. This dose range was chosen in view of the high effect of KAN0441571 measured in laboratory studies and the long circulation time of the substance that has been measured in blood (over 10 hours).

After 13 days (and four treatment days), the number of ROR1-bearing human cancer cells in the lymphatic system (spleen sample) decreased by about 50% compared to control-treated animals. This effect is statistically significant (P < 0.0005) as is also the desired decrease in spleen weight (P < 0.0002). The results also indicate that KAN0441571 was well tolerated and gave a long-acting effect against chronic lymphocytic leukemia in this disease model that closely resembles human disease.

Kanceras KAN0441571 acts on cancer cells mainly by causing cell death by self-destruction, so called apoptosis. The research that has resulted in the production of KAN440571 is based on an assay method that identifies ROR1 inhibitory substances. Thereafter, an optimization of the cell kill effect has been carried out using leukemic cells from patients (and corresponding cells from healthy donors). This optimization process has meant that the effect of substances like KAN0441571 has been spread to several target cells in the cancer cell. Kancera has been able to verify that the total effect of KAN0441571, in addition to an inhibition of ROR1, also includes regulation of mechanisms that control cell division and inflammation signals. This pattern of effects can help Kancera identify cancers that are particularly sensitive to the substance.

About the ROR project
ROR is a family of receptors: ROR-1 and ROR-2. The ROR receptors convey signals for growth and survival. Initially, ROR was linked to fetal development, but nowadays it is known that they also contribute to the development and spread of cancer cells. Kancera and Professor Håkan Mellstedt and his colleagues at Karolinska Institutet have shown that Kancera’s ROR inhibitor is capable of killing tumor cells from tumors in the pancreas, lungs, leukemia cells and multiple myeloma cells. Researchers have also shown that ROR is active and a target in prostate, breast and ovarian cancer.

Kancera and Professor Mellstedt have shown that inhibition of ROR causes cancer cells to eliminate themselves via cellular suicide. The efficiency of eliminating cancer cells has also been optimized against cells in patient samples. Thus, the ROR inhibitors have been directed at several targets in the cancer which together add up to the desired effect. In addition to effect against ROR1, Kancera has shown that the company’s ROR inhibitor also works by controlling cell division and inflammation signals. A more effective activity against cancer cells compared to healthy cells has been ensured by continuously investigating the pattern of effects in samples from patients and healthy donors. Against this background, there is reason to believe that a ROR-targeted drug is both safer and more effective than non-selective chemotherapeutic agents that are currently used to treat cancer.

On October 3, 2017 Nimbus Therapeutics, a biotechnology company applying deep computational expertise throughout drug discovery and development, reported the initiation of a long-term strategic alliance with Celgene Corporation (NASDAQ: CELG) in immunology (Press release, Nimbus Therapeutics, OCT 3, 2017, View Source [SID1234527305]).

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Under the terms of the agreement, Celgene will receive an option to acquire each program in the alliance up through a clinical inflection point. Nimbus will receive an upfront payment and potential downstream milestone payments for each program Celgene chooses to acquire. Nimbus will retain full control of research and development activities for each program prior to the program’s option point. Financial terms will remain undisclosed until Celgene acquires a program.

The Nimbus programs covered under the alliance include a preclinical effort targeting Tyk2 (tyrosine kinase 2), a signal-transduction kinase for key pro-inflammatory cytokine receptors, including IL-23, IL-12 and type-I interferons. Because of its central role in the inflammatory response, Tyk2 is a high-potential target for the treatment of autoimmune disorders including rheumatoid arthritis, lupus, Crohn’s disease, psoriasis and multiple sclerosis. The alliance also covers Nimbus’ preclinical small-molecule STING (stimulator of interferon genes) antagonist program, which seeks to block the role played by STING in the activation of the innate immune system in lupus and other interferonopathies. Nimbus will continue to own and develop its small-molecule STING agonist program for immuno-oncology, which is not part of the agreement.

"Celgene is committed to the continued growth of our expanding immunology and inflammation pipeline, and believes that the Nimbus immunology programs, including their efforts on Tyk2 and STING antagonists, represent important additions as we work to create the next generation of drug candidates for patients with autoimmune disorders," said Rupert Vessey, F.R.C.P., D.Phil., Executive Vice President and President, Global Research and Early Development, of Celgene.

Robert Plenge, M.D., Ph.D., Vice President, Research and Early Development, and Head, Inflammation and Immunology Thematic Center of Excellence, of Celgene, added, "We are excited about the potential of the Nimbus immunology targets, which are based on compelling human genetic data. Moreover, Nimbus’ robust in silico-based approach is very promising."

"We are thrilled to partner with Celgene and its world-renowned inflammation and immunology team to fuel the rapid advancement of these important potential therapeutic programs for patients," said Donald Nicholson, Ph.D., Chief Executive Officer of Nimbus. "In addition, our agreement with Celgene accelerates our growth as a company back into the clinic, while also expanding the breadth of our pipeline."