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CytomX Therapeutics Acquires Technologies Developed by Agensys

Clinical-stage and oncology-focused biopharmaceutical company CytomX Therapeutics, pioneering a novel class of investigational antibody therapeutics based on its Probody™ therapeutic technology platform, has acquired drug-conjugate linker-toxin and CD3-based bispecific technologies from Agensys, an affiliate of Astellas Pharma.

Under the terms of the agreement, CytomX will pay Astellas a one-time, up-front payment.

“The clinical progress we reported throughout 2018 provided initial proof of concept for our Probody therapeutic platform. This transaction with Astellas provides us with novel payloads and CD3 binding moieties for our next wave of potent anti-cancer agents that leverage our technology, including Probody drug conjugates and Probody T-cell engaging bispecifics,” explained W. Michael Kavanaugh, M.D. chief scientific officer and head of research and non-clinical development at CytomX.

Pipeline
Probody therapeutics developed by CytomX are designed to exploit unique conditions of the tumor microenvironment to more effectively localize antibody binding and activity while limiting activity in healthy tissues.

The company and its partners have four programs in the clinic, includes cancer immunotherapies against clinically-validated targets, including a PD-L1-targeting Probody therapeutic (CX-072), a PD-1-targeting Probody therapeutic (CX-188) and a CTLA-4-targeting Probody therapeutic (BMS-986249) being developed in collaboration with partnered with Bristol Myers Squibb.

The pipeline also includes first-in-class Probody-drug conjugates against highly attractive targets including a CD166-targeting Probody-drug conjugate wholly owned by CytomX (CX-2009), and a CD71-targeting Probody drug conjugate partnered with AbbVie (CX-2029).

CD166 and CD71 are among cancer targets that are considered to be inaccessible to conventional antibody-drug conjugates due to their presence on many healthy tissues.

In addition to its wholly owned programs, CytomX has strategic collaborations with AbbVie, Amgen, Bristol-Myers Squibb and ImmunoGen, Inc.

PROCLAIM-072 Trial
In November 2018 CytomX presented clinical translational data from PROCLAIM-072, an ongoing Phase I/II, open-label, dose-finding trial evaluating CX-072, a Probody therapeutic targeting PD-L1, in a poster at the 33rd Annual Meeting of The Society for Immunotherapy of Cancer (SITC) being held in Washington DC, USA.[1]

The PROCLAIM trial (Probody Clinical Assessment In Man) is an international umbrella program designed to evaluate CytomX’s Probody therapeutics. The first trial in this program, PROCLAIM-CX-072,  evaluates CX-072 as monotherapy and in combination with ipilimumab (Yervoy®; Bristol-Myers Squibb) or vemurafenib (Zelboraf®; Genentech/Roche ) in patients with metastatic or locally advanced unresectable solid tumors or lymphomas.

As part of the trial, participating patients received escalating doses of CX-072 from 0.3 mg/kg to 30 mg/kg. Biopsies were obtained from a subset of PROCLAIM-CX-072 patients during screening and at either 3-5 days after the first dose or after 4-6 weeks of CX-072 therapy. The presence of protease activity, CX-072 cleavage and activation, and measures of biological activity were assessed within tumors.

Results showed that protease activity was detected in the majority of patient biopsy samples (15 of 18 (83%)). Further, CX-072 was cleaved and activated within tumors, with the total amount of activated CX-072 increasing with dose. Doses of ≥ 3 mg/kg of CX-072 were estimated to achieve ≥ 98% PD-L1 target occupancy in patient tumors and attained concentrations that are associated with efficacy in a preclinical model. 7 of 12 evaluable patient biopsies showed an increase in tumor infiltration of CD8+ T cells, an activity consistent with the inhibition of the PD-1/PD-L1 signaling pathway.

“The preliminary data provide additional proof-of concept for the Probody platform and build upon the clinical data we have presented to date showing that CX-072 appears to be performing as designed in patients,” Kavanaugh noted

“These findings confirm that CX-072 is unmasked and activated and has biological activity in patient tumors while remaining predominantly masked and intact in circulation. This is another important step in understanding the full potential of our novel platform,” he concluded.

Reference
[1] PROCLAIM-CX-072: A Trial to Find Safe and Active Doses of an Investigational Drug CX-072 for Patients With Solid Tumors or Lymphomas – NCT03013491 


Last Editorial Review: January 8, 2019

Featured Image: Life scientists researching in laboratory. Courtesy: © 2010 – 2019 Fotolia. Used with permission.

Copyright © 2019 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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Cutting-Edge Science: Personalized Drug Screening for Multiple ​Myeloma​

In the decades old “war” against cancer, scientist are increasingly developing ore and better ways to help doctors address the unmet medical needs of patients with cancer. In addition to identifying new genetic mutations in different cancers, scientists are developing new ways to sequence tumors.  However, drawing on novel scientific and technological development they are now finding methods to more accurately match specific cancer treatments tailored to the exact needs of the patient’s particular cancer. This approach is often referred to a personalized therapy or precision medicine.

This hard work is showing interesting results.  In the treatment of multiple myeloma for example, scientists have developed a personalize method for testing the effectiveness of drugs. With the new tests doctors may predict quickly and more accurately the best treatments for individual patients. The novel approach, developed by scientists at Washington University School of Medicine​ in St. Louis, also may aid patients with leukemia or lymphoma.

Photo 1.0: Pilar de la Puente, PhD (left), and Kareem Azab, PhD, of Washington University School of Medicine in St. Louis, have developed a screening tool that may predict quickly and more accurately the best treatments for individual patients with multiple myeloma. The 3-D tissue-engineered bone marrow (3DTEBM) cultures pictured were developed with bone marrow samples to help determine which treatments are most effective.
Photo 1.0: Pilar de la Puente, PhD (left), and Kareem Azab, PhD, of Washington University School of Medicine in St. Louis, have developed a screening tool that may predict quickly and more accurately the best treatments for individual patients with multiple myeloma. The 3-D tissue-engineered bone marrow (3DTEBM) cultures pictured were developed with bone marrow samples to help determine which treatments are most effective.

The new test is unique in many ways.  The screening method suggests which commonly prescribed multiple myeloma drug, or combination of drugs, a physician should consider first for a particular patient.  n addition to suggesting the optimal drug and drug combination, the novel test also suggests the optimum dosage. A study validating the new method will be published in the December 2015 issue of the journal Biomaterials and now is available online.[1]

More effective
The method also is being evaluated in a clinical trial involving patients with multiple myeloma. The results will indicate if the method is more effective than current screening methods. “Even before the patient completes all of the MRIs, CT scans and other imaging procedures following diagnosis, we can have a recommendation for which drug and dosage to prescribe,” explained Kareem Azab​, Ph.D, an assistant professor of radiation oncology at the School of Medicine and the Siteman Cancer Center​ member who leads the research. “The test results come in three to four days,”​ Azab continued.​​​​​

Incidence
Multiple myeloma is a cancer of the infection-fighting plasma cells, part of the immune system found mainly in bone marrow.  The immune system, designed to fight infections and other diseases and is made up of several types of cells that work together. Lymphocytes, including T cells and B cells, are the main cell types of the immune system.

The disease is relatively uncommon cancer. The lifetime risk of getting multiple myeloma in the United States is 1 in 143 (0.7%). However, according to according to the American Cancer Society, an estimated 26,850 U.S. residents will still be diagnosed with the disease and about 11,240 patients are expected to die of the disease this year, second most prevalent hematological malignancy. Half of multiple myeloma patients diagnosed in the earliest stage of the disease don’t survive beyond about five years after initial treatment because the cancer becomes resistant to treatments.[2]  And despite the introduction of novel treatments, the disease remains incurable.

Treatment options
Treating multiple myeloma is difficult because in 90% of cases there is no obvious genetic mutation that can be targeted with treatment. Also, standard drug screening methods do not adequately recreate the environment surrounding cancer cells growing in a particular patient’s body.  This makes these methods less reliable at predicting effective drug therapies.

“Based on the observed discrepancy between preclinical and clinical outcomes we’ve concluded that this can be attributed to the failure of classic two-dimensional culture models to accurately recapitulate the [very] complex biology of multiple myeloma as well as drug responses observed in patients,” noted Pilar de la Puente, Ph.D from the Department of Radiation Oncology, Cancer Biology Division, Washington University School of Medicine.

Personalized drug screening
Azab and his colleagues, including De la Puente, the  hope that a more personalized approach will improve long-term patient outcomes. The method relies on 3-D tissue-engineered bone marrow cultures, also known as 3DTEBM, that Azab and his colleagues developed using myeloma patients’ bone marrow samples.

To more closely mimic outside the body what goes on within, scientists take small samples of a patient’s cells – cancerous and benign – and remodel them in the lab. This tumor “microenvironment” includes the cancer cells and other neighboring blood vessels, immune cells and other components whose interaction can help or inhibit the tumor cells’ growth.

Following this process, drugs are tested on the remodeled patient cells to determine which treatment is likely to be most effective.

This novel approach gauges the sensitivity of a patient’s cells to different drugs at any time in the course of the disease. “Therefore, as a patient’s multiple myeloma becomes more resistant to particular drugs, continued drug screening could suggest when to change therapies. This could save valuable time,” Azab explained. “Now we have a drug test that closely replicates what’s going on with a patient at any given moment. We think this method has a better chance of working than existing options,” he further noted.

New company
Azab and his colleagues have launched a new company, Cellatrix, in coordination with Washington University’s Office of Technology Management and BioGenerator, a nonprofit organization that helps area bioscience companies form.

The potential of the testing method has been noted by a number of medical and industry leaders. Later this year, Cellatrix will begin testing potential therapies on behalf of pharmaceutical companies. Azab’s team also is studying how well the screening method works for patients with leukemia or lymphoma.

When successful, Azab and his colleagues have won another battle in the ongoing struggle to conquer cancer, opening the way to better and more precise target treatment options.


Last Editorial Review: November 19, 2015

Photo: Pilar de la Puente, PhD (left), and Kareem Azab, PhD, of Washington University School of Medicine/St. Louis. (ADCs) Courtesy: © 2015 Robert Boston/Washington University School of Medicine/St. Louis. Used with permission.

Copyright © 2015 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

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