On May 29, 2020 Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, reported the presentation of two new studies at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting demonstrating the ability of Myriad’s riskScore test to provide personalized breast cancer risk information that allows patients and physicians to make better informed clinical treatment decisions (Press release, Myriad Genetics, MAY 29, 2020, View Source [SID1234561736]).

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"We are excited to further demonstrate Myriad’s commitment to providing the best possible risk assessment tools to patients through innovation," said Nicole Lambert, president of Myriad Oncology, Myriad Women’s Health and Myriad International. "The validation data we are presenting at ASCO (Free ASCO Whitepaper) this year will support a broader launch of riskScore to even more women in the coming year with more personalized information and the unique ability to modify carrier risk through a clinically validated tool."

Summaries of the studies are below. Follow Myriad on Twitter via @myriadgenetics and keep up to date with ASCO (Free ASCO Whitepaper) meeting news and updates by using the #ASCO20 hashtag.

riskScore Presentations at 2020 ASCO (Free ASCO Whitepaper):

Title: Comprehensive breast cancer (BC) risk assessment for CHEK2 carriers incorporating a polygenic risk score (PRS) and the Tyrer-Cuzick (TC) model
Presenter: Mark E. Robson, MD, Memorial Sloan Kettering Cancer Center
Location: View Source

In this study, 358,471 women with hereditary cancer risk who were tested with a multigene panel were assessed to find 4,331 women who were carriers of deleterious CHEK2 mutations. These patients were used to develop a mathematical model to assess risk status using family history information and Myriad’s riskScore test. This model was then validated in an independent cohort of 459 women. In CHEK2 pathogenic variant carriers, a significant correlation was detected of CHEK2 status with family history (FH) (p=4.1 × 10-17) and of polygenic risk scores with FH among CHEK2 carriers (p=1.7× 10-5). Among the patients in the validation cohort, 24.0% of CHEK2 carriers were categorized as low risk (<20%), and 62.6% were categorized as moderate risk (20-50%). For 13.4% of CHEK2 carriers, risk estimation incorporating PRS and TC generated BC risks of greater than 50%, consistent with genes recognized as highly penetrant.

To view Graph 1: Precision Breast Cancer Risk Categorization of CHEK2 Carriers, please visit the following link:
View Source

Title: Performance of the IBIS/Tyrer-Cuzick (TC) Model by Race/Ethnicity in the Women’s Health Initiative
Presenter: Allison W. Kurian, M.D., M.Sc, Stanford University
Location: View Source

In this study, 91,893 women of differing racial identities with no personal history of breast cancer were followed for a median of 18.9 years to assess incidence of breast cancer. 6,836 new cases of breast cancer were diagnosed among the women. The Tyrer-Cuzick model was used to assess risk of breast cancer and then actual cases of breast cancer were compared to expected cases based upon the Tyrer-Cuzick risk assessment. The study found that the Tyrer-Cuzick model was an accurate predictor of breast cancer risk among various ethnicities except for Hispanic women where it overestimated breast cancer risk (ratio of observed versus expected cases overall was 0.95).

About riskScore
riskScore is a new clinically validated personalized medicine tool that enhances Myriad’s myRisk Hereditary Cancer test. riskScore helps to further predict a women’s lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from more than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

About Myriad myRisk Hereditary Cancer
The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 35 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

On May 29, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported at the ASCO (Free ASCO Whitepaper) Annual Meeting presented a preclinical update for its novel, clinical-stage, selective RET-inhibitor drug candidate, TPX-0046 (Press release, Turning Point Therapeutics, MAY 29, 2020, View Source [SID1234564371]).

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In the updated preclinical studies comparing proxy molecules for approved and investigational RET inhibitors, TPX-0046 demonstrated potent in vitro and in vivo activity against a range of RET alterations, including greater potency against solvent-front mutations, G810S, G810R, G810C and G810N.

A phase 1/2 trial of TPX-0046 in RET TKI-naïve and -pretreated patients is ongoing.

"TPX-0046 was designed as a potent RET inhibitor with the potential to address TKI-naïve and RET inhibitor-resistant RET-dependent cancers," said Alexander Drilon, M.D., medical oncologist and acting chief of the Early Drug Development Service, Memorial Sloan Kettering Cancer Center, and a principal investigator for the TPX-0046 clinical study. "Specifically, in preclinical studies, TPX-0046 inhibited RET solvent front mutations that have been observed in biopsies from patients with progression on a prior RET inhibitor. Developing a next-generation RET inhibitor is an unmet need."

In enzymatic and cellular assays presented at ASCO (Free ASCO Whitepaper), TPX-0046 was potent against wildtype RET and multiple RET mutations and fusions.TPX-0046 also demonstrated antitumor activity in RET-driven cell-derived and patient-derived xenograft tumor models, including those that harbor a RET G810R solvent-front mutation.

The ongoing Phase 1/2 open-label, single-arm, multi-center clinical study of TPX-0046 is enrolling TKI-naïve and -pretreated patients with RET-altered non-small-cell lung, thyroid, and other advanced cancers in a Phase 1 dose escalation study of approximately 50 patients, and Phase 2 expansion study of approximately 300 patients with multiple cohorts, to assess safety, tolerability, pharmacokinetics (PK) and clinical activity. The study design allows intra-patient dose escalation based on tolerability. For more information, visit clinicaltrials.gov and search NCT04161391.

"The preclinical studies we are presenting today support a potential role for TPX-0046 in both TKI-naïve and TKI-pretreated patients," said Athena Countouriotis, M.D., president and chief executive officer of Turning Point Therapeutics. "With a compact design, and lower molecular weight than other investigational or approved RET inhibitors, TPX-0046 has shown encouraging preclinical activity against multiple RET G810 mutations, where there are currently no approved therapeutic options for patients."

TPX-0046 is a multi-targeted RET and SRC kinase inhibitor with a novel three-dimensional macrocyclic structure that is smaller and structurally distinguished from other approved or investigational RET inhibitors. Activation of RET– a receptor tyrosine kinase –through gain-of-function mutations or fusions has been found in multiple tumor types, including non-small-cell lung and thyroid cancers. In preclinical studies TPX-0046 spared vascular endothelial growth factor (VEGF) receptors 1, 2 and 3. According to research published in the European Journal of Cancer1, hypertension was the most common adverse effect (up to 46 percent) among multiple anti-cancer therapeutics that inhibit VEGF. Dual inhibition of RET and SRC represents a novel therapeutic strategy to target abnormal RET signaling in cancers. Inhibition of SRC family kinases has the potential to reduce bypass resistance from signaling through multiple receptor tyrosine kinases and therefore has the potential to increase the therapeutic effect of TPX-0046.

On May 29, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion under conditional marketing authorisation for Rozlytrek (entrectinib) for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, who have no satisfactory treatment options (Press release, Hoffmann-La Roche, MAY 29, 2020, View Source [SID1234558664]). The CHMP has also recommended Rozlytrek for the treatment of adults with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.1

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"Once approved, Rozlytrek could become Roche’s first tumour-agnostic therapy in Europe," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "This milestone therefore represents additional progress in personalised healthcare. Based on genomic testing, Rozlytrek provides an effective first-line treatment for many people whose cancers harbour NTRK or ROS1 gene fusions, including tumours that have progressed to the brain."

The positive CHMP opinion is based on results from the integrated analysis of the pivotal phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials, and data from the phase I/II STARTRK-NG study. Results showed:

Rozlytrek shrank tumours in more than half of people with NTRK fusion-positive, locally advanced or metastatic solid tumours (overall response rate [ORR]= 63.5%; N=74), and objective responses were observed across 14 tumour types (median duration of response [DoR] = 12.9 months [9.3 months – not reached], N=21 out of 47).2
In ROS1-positive, advanced NSCLC, Rozlytrek shrank tumours in 73.4% of people with the disease (ORR; N=94 with 12 months follow up), with a median DoR of 16.5 months (14.6 – 28.6 months). In a group of 161 patients with 6 months follow up, including 29% of patients with central nervous system (CNS) metastases at baseline, ORR was observed to be 67.1%.1
Objective responses to Rozlytrek were seen in people with CNS metastases at baseline, in both the NTRK and ROS1 populations.1,2
In paediatric patients, Rozlytrek shrank tumours (ORR) in all children and adolescents who had NTRK gene fusions (N=5), with two achieving a complete response (CR). Two patients with primary high-grade tumours in the CNS had objective responses, including one patient with a CR.1
Across these studies, Rozlytrek was evaluated in several solid tumour types, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers and neuroblastoma.1,2

Rozlytrek was well tolerated. The most common adverse reactions (≥20 percent) with Rozlytrek were fatigue, constipation, altered sense of taste (dysgeusia), swelling (oedema), dizziness, diarrhoea, nausea, nervous system disorders (dysaesthesia), shortness of breath (dyspnoea), anaemia, increased weight, increased blood creatinine, pain, cognitive disorders, vomiting, cough, and fever (pyrexia).1,2

Rozlytrek has been granted Priority Medicines (PRIME) designation by the EMA for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or who have no acceptable standard therapies.1 A final decision regarding the approval of Rozlytrek by the European Commission is expected in the coming months.

Biomarker testing for NTRK gene fusions and ROS1 in NSCLC across all solid tumours is the only way to identify people who are most eligible for treatment with Rozlytrek. Roche is leveraging its expertise in developing personalised medicines and advanced diagnostics, in conjunction with Foundation Medicine, to develop a companion diagnostic that will help identify people with NTRK and ROS1 gene fusions.

About the integrated analysis
The CHMP recommendation is based on an integrated analysis including data from 74 people with locally advanced or metastatic NTRK fusion-positive solid tumours (14 tumour types) and 161 people with ROS1-positive NSCLC from the phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials.1,2 It is also based on data from the phase I/II STARTRK-NG study in paediatric patients.1 The studies enrolled people across 15 countries and more than 150 clinical trial sites. Safety was assessed from an integrated analysis of 504 people across these four trials.1,2

About NTRK fusion-positive cancer
NTRK fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signalling pathways involved in the proliferation of certain types of cancer.3 NTRK gene fusions are present in tumours irrespective of site of origin. These fusions have been identified in a broad range of solid tumour types, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers and neuroblastoma.2

About ROS1-positive NSCLC
ROS1 is a tyrosine kinase, which plays a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, cancer cells grow and proliferate in an uncontrolled manner. Blocking this abnormal signalling can cause tumour cells to shrink or die.4

ROS1 gene fusions account for 1-2% of non-small-cell lung cancer (NSCLC).4 Lung cancer is the leading cause of cancer-related death across the world.5 Each year, more than one and a half million people die as a result of the disease globally, equating to more than 4,000 deaths every day.5 NSCLC is the most common type of lung cancer and accounts for up to 85% of all lung cancer diagnoses.6 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 gene fusions.4

About Rozlytrek
Rozlytrek (entrectinib) is a tumour-agnostic, once-daily oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.7,8 Rozlytrek can block NTRK and ROS1 kinase activity and may result in the death of cancer cells with NTRK or ROS1 gene fusions.7,8

Rozlytrek was granted accelerated approval in August 2019 by the US Food and Drug Administration (FDA), following receipt of Breakthrough Therapy designation, for the treatment of adult and paediatric patients 12 years of age and older with solid tumours that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy, and was approved for the treatment of adults with ROS1-positive, metastatic NSCLC. In June 2019, Rozlytrek was also approved by Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of adult and paediatric patients with NTRK fusion-positive, advanced recurrent solid tumours, and was later approved in ROS1 positive NSCLC in February 2020. Rozlytrek has also received approvals by health authorities in Australia, Canada, Hong Kong, Israel and South Korea.1

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

On May 29, 2020 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody therapeutic technology platform, reported the availability of oral and poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program taking place from May 29 – May 31, 2020 (Press release, CytomX Therapeutics, MAY 29, 2020, View Source [SID1234558680]).

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"A comprehensive body of evidence was presented today at ASCO (Free ASCO Whitepaper) 2020 that continues to validate our approach to conditional antibody activation and therapeutic target engagement with the Probody platform," said Amy Peterson, M.D., chief development officer of CytomX Therapeutics. "The seven presentations collectively highlight the potential of the Probody platform to enable successful engagement of previously undruggable targets, like CD71 and CD166, and create next generation immune-checkpoint inhibitors such as the anti-PD-L1 Probody therapeutic, CX-072, and BMS-986249, a Probody version of ipilimumab. The findings underpin the advancement of all four drug candidates into Phase 2 and our commitment to bringing meaningful advances to patients living with cancer."

CX-2029: Validating CD71 As A First-in-Class Oncology Target

In the oral abstract 3502, Dr. Melissa Johnson of the Sarah Cannon Research Institute at Tennessee Oncology, presented preliminary clinical data from the first-in-human, dose-escalation, monotherapy Phase 1 study of CX-2029, a Probody drug conjugate (PDC) targeting CD71 (transferrin receptor). CX-2029 is conjugated to the cytotoxic payload MMAE and is being developed by CytomX in partnership with AbbVie. As of an April 20, 2020 data cutoff, 45 patients with advanced solid tumors were enrolled into 8 escalating dose cohorts between 0.1 mg/kg – 5 mg/kg CX-2029 administered intravenously every three weeks.

Evidence of target lesion reduction was seen, principally in patients with tumors of squamous histology. (Figure 1)
° 3 confirmed partial responses were observed in 17 response-evaluable patients treated at doses ≥2 mg/kg of CX-2029, 2 in patients with squamous non-small cell lung cancer (SqNSCLC) and 1 in a patient with head and neck squamous cell cancer (HNSCC).
° 2 of the partial responses (both at the 3 mg/kg dose) were confirmed after the April 20th cutoff date.
CX-2029 Waterfall Plot (Doses 2–5 mg/kg)

CX-2029 Waterfall Plot (Doses 2–5 mg/kg)
Figure 1 is available at View Source

Safety Profile Supports Recommended Phase 2 Dose of 3 mg/kg, Every Three Weeks

CX-2029 was generally well tolerated at doses up to 3 mg/kg.
At doses of 0.25 – 5 mg/kg, CX-2029 circulated predominantly as the intact species (>90%).
The most common treatment related adverse events (TRAE) were infusion related reactions, anemia, and neutropenia/leukopenia.
° Infusion related reactions were mostly Grade 1/2, occurred at the first dose, were not dose dependent and resolved upon initiation of supportive care.
° Hematologic TRAEs Grade ≥ 3 were dose dependent.
• Anemia and neutropenia are commonly observed with the MMAE payload.
• Anemia was managed with transfusions and supportive care.
No CX-2029 treatment related deaths were reported and late onset Grade 3/4 TRAEs were predominately anemia and neutropenia.
The etiology of anemia is under investigation and is likely multifactorial, including MMAE-related and CD71 expression on red blood cell precursors.
CytomX is preparing to advance the dose of 3 mg/kg of CX-2029 administered every 3 weeks into 4 dose-expansion cohorts: HNSCC, SqNSCLC, esophageal carcinoma and diffuse large B cell lymphoma.
"Targeting CD71 with this novel approach has the potential to address areas of unmet medical need in difficult to treat tumor types, improving patient benefit," said Melissa L. Johnson, M.D., CX-2029 principal study investigator and associate director of lung cancer research at Sarah Cannon Research Institute at Tennessee Oncology. "This first-in-human data of CX-2029 establishes the transferrin receptor as a high potential anticancer target addressable with CytomX’s Probody technology."

CX-2009: Encouraging Clinical Activity Supports Advancement in HER2 Negative Breast Cancer

In Poster 18, Dr. Valentina Boni of START Madrid-CIOCC, presented updated data on CX-2009, a PDC targeting CD166 and conjugated to the cytotoxic payload DM4. As of an April 20, 2020 data cutoff, 96 patients were enrolled into the dose escalation Phase 1 study and received CX-2009 at escalating doses of 0.25 – 10 mg/kg every 3 weeks (86 patients) or 4 – 6 mg/kg every 2 weeks (10 patients).

Durable Clinical Activity Observed in HER2 Negative (HER2-) Breast Cancer

Evidence of target lesion reduction was observed at doses or dose equivalents of ≥4 mg/kg every 3 weeks across 68 evaluable patients including those with HER2- breast cancer, ovarian cancer, NSCLC and HNSCC.
° HER2- breast cancer patients were heavily pretreated with a median of 7 prior lines of therapy.
26 patients with HER2– breast cancer who received ≥4 mg/kg of CX-2009 were response-evaluable:
° 2 confirmed partial responses were observed, both in patients with hormone receptor positive (HR+) breast cancer.
° 3 unconfirmed responses were observed in patients with triple negative breast cancer (TNBC).
° Clinical benefit rates of 39% and 35% were observed at 16 and 24 weeks (CBR16 and CBR24, respectively).
• All 4 TNBC patients who achieved CBR16 also achieved CBR24.
CX-2009 Waterfall Plot and Spider Plot: HER2- Breast Cancer (≥4 mg/kg Every 3 Weeks)

CX-2009 Waterfall Plot and Spider Plot
Figure 2 is available at View Source

Safety Profile Supports Recommended Phase 2 Dose of 7mg/kg, Every 3 Weeks

CX-2009 was generally well tolerated at doses up to 7 mg/kg administered every three weeks.
No dose limiting toxicities (DLTs) were reported at doses up to 7 mg/kg.
DM4-related toxicities, including ocular, neuropathic, and hepatic were higher in frequency at dose equivalents greater than 7 mg/kg dosed at every three weeks compared to 7 mg/kg or lower.
° Occurrence and severity of ocular adverse events were dose dependent: One Grade 3+ event was observed in a patient treated at 5 mg/kg, none at 7 mg/kg.
° 20% of patients dosed at ≥8 mg/kg experienced Grade 3+ ocular adverse events.
Preliminary pharmacokinetic (PK) data showed that CX-2009 circulates predominantly intact at all doses and PK is not strongly influenced by target-mediated drug disposition or anti-drug antibodies (ADAs). (Poster 329)
In December 2019, CytomX announced the initiation of a Phase 2 expansion study of CX-2009 monotherapy at 7 mg/kg administered every three weeks in up to 40 patients with hormone receptor (ER, PR) positive, HER2 negative breast cancer. In March 2020, CytomX announced the decision to temporarily pause new patient enrollment and new site activation in this study due to the impact of the COVID-19 pandemic. CytomX continues to closely monitor emerging Health Authority guidance and IRB/Ethics Committee recommendations and intends to resume the CX-2009 clinical program as soon as practicable.

"Patients with advanced breast cancer continue to need treatment options, this is especially true for patients with hormone receptor positive and HER2 negative breast cancer that is refractory to hormonal based therapies," said Alison L. Hannah, M.D., chief medical officer of CytomX Therapeutics. "We believe that targeting CD166, previously considered undruggable as an oncology target, using our Probody drug conjugate platform, may provide a unique treatment opportunity for this patient population. The data in patients with triple negative breast cancer are equally interesting and support the advancement of CX-2009 monotherapy into Phase 2 where we will also evaluate CX-2009 in combination with CX-072, our Probody therapeutic directed against PD-L1."

CX-072: Anti-PD-L1 Probody Checkpoint Inhibitor

In the oral presentation of Abstract 3005 by Dr. Fiona Thistlethwaite of The Christie NHS Foundation Trust at the University of Manchester, updated data were presented from the Phase 1/2 trial of PROCLAIM-CX-072 monotherapy and CX-072 in combination with ipilimumab with a focus on patients who received long-term treatment, defined as ≥ 6 months of treatment. The CX-072 10 mg/kg monotherapy expansion arm enrolled 114 patients in seven tumor types.

As of an April 20, 2020 data cutoff, CX-072 monotherapy continued to demonstrate durable anti-tumor activity in patients with IO sensitive tumors such as TNBC, anal squamous cell carcinoma (aSCC), cutaneous squamous cell carcinoma (cSCC) and tumors with high mutational burden (hTMB).
As of the same data cutoff, CX-072 in combination with ipilimumab had been administered to 27 patients with advanced solid tumors. Durable anti-cancer activity was observed including one complete response in a patient with aSCC who remains on study more than two years after first dose.
Of the 141 patients across the monotherapy and combination arms: 34 patients received long term treatment in the monotherapy arm (median 11.3 months), and 6 patients received long term treatment in the combination arm (median 21.3 months).
Grade 3/4 TRAEs were 10% and 5.9% for who received monotherapy < 6 months and ≥ 6 months, respectively, and 33% in each group in the combination arm.
Long term patients experienced fewer irAEs and had no grade 3+ irAEs suggesting that tolerability early on can impact duration of treatment.
Preliminary clinical PK data (Poster 332) and translational analyses of pre- and on-treatment biopsies (Poster 172) were supportive of the Probody mechanism of action.
CX-072 Monotherapy Waterfall Plots and Spider Plots (10 mg/kg)

CX-072
Figure 3 is available at View Source

Continued Dr. Hannah "Our ASCO (Free ASCO Whitepaper)20 clinical, translational, and pharmacokinetic presentations on CX-072 reinforce previously presented data and show clear evidence of anti-cancer activity and favorable tolerability for this unique checkpoint inhibitor. These integrated data support a differentiated profile for CX-072 that we believe can be of potential utility as a unique combination partner for other anti-cancer agents, including CX-2009."

BMS-986249: Anti-CTLA-4 Probody Demonstrates Encouraging Safety Profile in Phase 1 Trial

Bristol Myers Squibb presented dose escalation data from their Phase 1/2 trial of BMS-986249, a Probody version of the anti-CTLA-4 antibody ipilimumab in Abstract 3508. This trial assessed the safety, pharmacokinetics and pharmacodynamics of escalating doses of BMS-986249 as monotherapy or in combination with the anti PD-1 antibody nivolumab in patients with advanced cancers. The doses of BMS-986249 ranged from 240 mg to 2400 mg (approximately 3 – 30 mg/kg). BMS-986249 was generally well tolerated as monotherapy and in combination with nivolumab. Bristol Myers Squibb has initiated a randomized clinical trial to explore various doses of BMS-986249 in combination with nivolumab in patients with advanced melanoma.

ASCO20 Virtual Scientific Program – Posters and Presentations

Copies of the ASCO (Free ASCO Whitepaper)20 presentations and posters are available under the Scientific Publications section of the CytomX website at www.CytomX.com.

Conference Call and Webcast

CytomX senior management will host a conference call and live webcast with slides today, Friday, May 29, 2020, from 5:00 p.m. – 6:00 p.m. ET/ 2:00 p.m. – 3:00 p.m. PT to discuss these presentations. This event can be accessed in three ways:

From the CytomX website: View Source Please access the website 15 minutes prior to the start of the call to download and install any necessary audio software.

By telephone: Participants can access the call by dialing 1-877-809-6037 (United States) or 1-615-247-0221 (International) referencing Conference ID 4267278.

By replay: A replay of the webcast will be located under the Investor Relations section of CytomX’s website approximately two hours after the conclusion of the live call and will be available for 30 days following the call.

On May 29, 2020 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported positive data from in vivo studies that show strong antitumoral efficacy with several of its INTASYL pipeline programs, including PH-762, PH-894 and PH-804 (Press release, Phio Pharmaceuticals, MAY 29, 2020, View Source [SID1234558696]). These results show that intratumoral delivery of INTASYL compounds inhibited tumor growth by overcoming the immunosuppressive tumor microenvironment (TME) as shown by changes in T cell composition and activation. Therefore, the Company believes these pipeline programs show great promise in the treatment of solid tumors. These data were presented during the ASCO (Free ASCO Whitepaper) 2020 Virtual Scientific Program (Abstract e15206: "Intratumoral use of self-delivering RNAi to reprogram the tumor microenvironment and boost the antitumor response").

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The Company’s pipeline programs PH-762, PH-894 and PH-804 are INTASYL compounds designed to silence the expression of PD-1, BRD4 and TIGIT, respectively, which are proteins linked to reduced immune cell function in cancer patients. A series of preclinical in vivo studies in tumor models were conducted and the resulting data showed dose-dependent attenuated tumor growth for the INTASYL compounds compared to control groups. Relevant changes in the TME include an increase of tumor-infiltrating lymphocytes, including CD8+ T cells, responsible for tumor cell killing, and an increase of activation markers on these cells. Together, these novel findings support using INTASYL intratumorally as a viable approach to immunotherapy and warrant further investigation in patients.

"These exciting new data show that INTASYL compounds are able to overcome the immunosuppressive TME by reprogramming T cells in order to inhibit tumor growth. These data support our belief that Phio’s INTASYL technology can be used to develop powerful immunotherapeutics, which can overcome the shortcomings of currently available systemic immunotherapy," said Dr. Simon Fricker, Phio’s VP of Research. "We look forward to continuing our development of INTASYL, including the IND enabling studies which are currently ongoing."

A poster further detailing the data presented at the ASCO (Free ASCO Whitepaper) 2020 Virtual Scientific Program will be made available under the "Investors – Events and Presentations" section of the Company’s website (click here).