On May 26, 2021 ADC Therapeutics SA (NYSE:ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, reported that results of the Phase 1 clinical trial of camidanlumab tesirine (Cami), an anti-CD25 ADC, in patients with relapsed or refractory Hodgkin and non-Hodgkin lymphomas have been published online in The Lancet Haematology (Press release, ADC Therapeutics, MAY 26, 2021, View Source [SID1234580605]).

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"There is a significant unmet medical need for novel therapies that improve outcomes in patients with relapsed or refractory Hodgkin lymphoma," said Mehdi Hamadani, MD, Professor of Internal Medicine at the Medical College of Wisconsin, Division of Hematology & Oncology and lead author of The Lancet Haematology paper. "This patient population is often heavily pretreated, as was the case in this published study in which patients experienced a median of five previous systemic therapies. The Phase 1 study demonstrates encouraging potential for Cami to provide a new treatment option for patients with relapsed or refractory Hodgkin lymphoma."

The multicenter, open-label, single-arm, dose escalation and dose expansion Phase 1 clinical trial enrolled 133 adult patients, 77 (58%) with classical Hodgkin lymphoma and 56 (42%) with non-Hodgkin lymphoma. Enrolled patients were required to have pathologically confirmed relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma and no therapies with established clinical benefit for their disease stage available to them.

"We’re pleased the results of our Phase 1 trial of Cami in patients with relapsed or refractory lymphoma have been published in The Lancet Haematology," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer at ADC Therapeutics. "The positive results in patients with Hodgkin lymphoma guided the design of our pivotal Phase 2 trial, which has completed enrollment. We’re continuing to follow patients and look forward to presenting data from the Phase 2 Cami trial at an upcoming congress."

Key results include:

In the total patient population, the overall response rate (ORR) was 58%, with 38 (29%) of 130 patients reported to have a complete response.
In heavily pretreated patients with Hodgkin lymphoma, across all doses, the ORR was 71%, with 32 (42%) of 77 patients reported to have a complete response.
In Hodgkin lymphoma patients who received 45 μg/kg (the recommended Phase 2 starting dose), the ORR was 86%, with 18 (49%) of 37 patients reported to have a complete response.
In Hodgkin lymphoma patients who received 30 μg/kg, the ORR was 55%, with seven (35%) of 20 patients reported to have a complete response.
In patients with non-Hodgkin lymphoma, the ORR was 38%, with five (9%) of 53 patients reported to have a complete response.
The overall median duration of response was 6.6 months for all patients with Hodgkin lymphoma and 7.2 months for Hodgkin lymphoma patients who received 45 μg/kg.
Cami demonstrated an acceptable safety profile. The most commonly observed adverse events included elevated liver enzymes (without hepatic synthetic dysfunction), rash, fatigue, oedema or effusion, and nausea.
Based on the data from this Phase 1 clinical trial, a Phase 2 trial to further evaluate the safety and efficacy of Cami in patients with relapsed or refractory Hodgkin lymphoma is ongoing. Interim data from the pivotal Phase 2 trial presented at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) meeting demonstrated encouraging antitumor activity as a single agent with an ORR of 83%, a complete response rate of 38% and no new safety signals. These data highlight the potential for Cami to address an unmet need in heavily pretreated patients (median of seven prior lines of systemic therapy).

For information about the ongoing pivotal Phase 2 clinical trial of Cami in patients with relapsed or refractory Hodgkin lymphoma, please visit View Source (identifier NCT04052997).

About Camidanlumab Tesirine (Cami)

Camidanlumab tesirine (Cami, formerly ADCT-301) is an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once bound to a CD25-expressing cell, Cami is internalized into the cell where enzymes release the PBD-based payload, killing the cell. This applies to CD25-expressing tumor cells and also to CD25-expressing Tregs. The intra-tumoral release of its PBD payload may also cause bystander killing of neighboring tumor cells, and PBDs have also been shown to induce immunogenic cell death. All of these properties of Cami may enhance immune-mediated anti-tumor activity.

Cami is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma and a Phase 1b clinical trial as monotherapy and in combination with pembrolizumab in solid tumors.

On May 25, 2021 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported that Raul Rodriguez, the company’s president and chief executive officer, is scheduled to present a company overview at the Jefferies Virtual Healthcare Conference on Wednesday, June 2, 2021 at 1:00 p.m. Eastern Time (Press release, Rigel, MAY 26, 2021, View Source [SID1234580621]).

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To access the live and subsequently archived webcast, go to the Investor Relations section of the company’s website at www.rigel.com. Please connect to Rigel’s website several minutes prior to the start of the live webcast to ensure adequate time for any software download that may be necessary.

On May 26, 2021 NiKang Therapeutics Inc. ("NiKang"), a clinical stage biotech company focused on developing innovative small molecule oncology medicines to help patients with unmet medical needs, reported the completion of an oversubscribed $200 million series C financing led by Cormorant Asset Management, HBM Healthcare Investments and Octagon Capital Advisors with participations from a premier syndicate of funds, including new investors EcoR1 Capital, Perceptive Advisors, Wellington Management, Ally Bridge Group, Pavilion Capital, funds and accounts managed by BlackRock, RA Capital Management, Surveyor Capital (a Citadel company), Samsara BioCapital, PFM Health Sciences, Invus, Janus Henderson Investors and Logos Capital (Press release, NiKang Therapeutics, MAY 26, 2021, View Source [SID1234580637]). All existing investors including CBC Group, RTW Investments, LP, Lilly Asia Ventures, Matrix Partners China, and Casdin Capital participated in the financing. In connection with the financing, Bing Yao, Ph.D., former CEO and chairman of Viela Bio, and Ting Jia, Ph.D., founder, and chief investment officer of Octagon Capital Advisors will join NiKang’s Board of Directors.

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"We are thrilled to have such an outstanding group of investors as our shareholders," said Zhenhai Gao, Ph.D., co-founder, president, and chief executive officer of NiKang. "Their support of our vision allows us to build the world’s leading precision oncology company. We are now well positioned to rapidly advance our pipeline into clinic including our differentiated HIF-2 alpha inhibitor, and to bring our company to the next level of growth."

"This financing is a testament to the quality of our science and team," Kelsey Chen, Ph.D., MBA, chief finance officer, added. "Since joining NiKang, I have witnessed the passion and dedication by a group of talented scientists who are devoting their lives to advancing treatments for patients. We are grateful to be recognized by such a high caliber group of investors."

"NiKang has made remarkable progress over the last eight months since our initial investment," said Ting Jia, Ph.D., chief investment officer of Octagon. "We are impressed by the team’s accomplishment. We believe NiKang’s unique approach of attacking difficult-to-drug targets offers promising opportunities in developing breakthrough treatments for cancer patients. We are excited to co-lead the series C financing and partner with the NiKang team to accelerate its growth."

"We are proud of what NiKang has achieved since its inception," said Sean Cao, executive chairman of NiKang and managing director of CBC Group, which incubated the company. "The strength of this group of investors validates NiKang’s achievements and demonstrates their confidence in NiKang’s potential to grow into a leading innovative drug company."

Proceeds will be used to advance the company’s lead drug candidates into the clinic, expand the pipeline and fund internal drug discovery programs.

On May 26, 2021 Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines, reported that Joseph Oliveto, President and Chief Executive Officer, will present at the Jefferies Virtual Healthcare Conference on Wednesday, June 2, 2021 at 4:00 PM ET (Press release, Milestone Pharmaceuticals, MAY 26, 2021, View Source [SID1234580653]). The conference will be held in a virtual meeting format.

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A live webcast of the presentation can be accessed in the News & Events section of Milestone’s website at www.milestonepharma.com. An archived replay of the webcast will be available on the same website following the presentation.

On May 26, 2021 Cleveland Clinic researchers reported that they have identified a promising drug target for treating and preventing aggressive, drug-resistant prostate cancer (Press release, Cleveland Clinic Foundation, MAY 26, 2021, View Source [SID1234583288]).

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Nima Sharifi, M.D.

The team, led by Nima Sharifi, M.D., of Cleveland Clinic’s Lerner Research Institute, demonstrated that inhibiting the protein H6PD led to significantly reduced tumor sizes and improved survival among mouse models with drug-resistant prostate cancer. The H6PD levels also were elevated in biopsied patient tumors, suggesting the protein might be targeted in patients for treatment.

"New treatment approaches for drug-resistant prostate cancer are desperately needed," said Dr. Sharifi, director of Cleveland Clinic’s Genitourinary Malignancies Research Center. "These findings suggest an entirely new strategy for treatment of men with this aggressive form of prostate cancer."

Enzalutamide, a current standard-of-care hormone therapy for metastatic prostate cancer, works by blocking androgen receptors, which are proteins that help drive cancer cells. While initially effective, most patients eventually develop resistance to the treatment. This resistance occurs when androgen receptors are blocked and cancer cells adapt to get their "fuel" from a similar receptor, called the glucocorticoid receptor.

These glucocorticoid receptors bind to and interact with the stress hormone cortisol. In an earlier study published in eLife, Dr. Sharifi and his team linked enzalutamide resistance to increased tumor cortisol levels. They found that tumors typically express a protein called 11β-HSD2, which inactivates cortisol. However, when this protein expression is inhibited in some tumors, cortisol and the glucocorticoid receptor are stimulated and become available for use by cancer cells.

"Taken together, our study findings suggest that pharmacologically inhibiting the H6PD protein can reverse drug resistance in prostate cancer cells," said Dr. Sharifi. "By blocking this protein, we are able to prevent cancer cells from utilizing their backup fuel supply – cortisol and its receptor. When we block this pathway, tumors begin to become responsive to standard treatments again."

In this new study, the researchers demonstrated that, in addition to decreased expression of 11β-HSD2, resistant tumors also have increased H6PD levels.

"With lower levels of 11β-HSD2, which normally functions to cut off the fuel supply to drug-resistant cancer cells, the cells are free to continue to grow and spread unchecked," said Dr. Sharifi. "By inhibiting the H6PD protein, however, we were able to reinstate anti-cortisol effects. This finding is key to better understanding how disruptions in cortisol metabolism contribute to cancer cells’ growth and spread."

Dr. Sharifi’s clinical collaborator Eric Klein, M.D., chair of Cleveland Clinic’s Urology & Kidney Institute and a co-author on the study, said, "We found elevated levels of H6PD in both animal models and patient tissues, particularly after treating tumors with enzalutamide. These findings hold promise for novel precision medicine approaches in the management of men with aggressive prostate cancer."

The researchers targeted H6PD with rucaparib, a drug already approved by the U.S. Food and Drug Administration. Dr. Sharifi collaborated with scientists from Cleveland Clinic’s Center for Therapeutics Discovery to identify what parts of rucaparib are chemically necessary to inhibit the protein.

Researchers administered enzalutamide to mouse models of aggressive prostate cancer that expressed H6PD and those where the protein was blocked with rucaparib. The models where H6PD was blocked had significantly smaller tumors and longer progression-free survival following enzalutamide treatment.

Jianneng Li, PhD, a post-doctoral fellow in Dr. Sharifi’s lab, is first author on the study, which was supported by the National Cancer Institute and the Prostate Cancer Foundation.

"These findings represent an exciting new opportunity to potentially reverse drug resistance in advanced prostate cancer," said Howard R. Soule, PhD, Executive Vice President and Chief Science Officer of the Prostate Cancer Foundation. "PCF commends Dr. Sharifi and the team on their achievement and proudly supports their work to bring us closer to our mission to eliminate death and suffering from prostate cancer."