On October 29, 2019 Inivata, a leader in liquid biopsy, and the European Organisation for Research and Treatment of Cancer (EORTC) have reported a collaboration in which Inivata’s InVisionFirst-Lung liquid biopsy test will be used in a Phase II trial to screen and monitor ALK positive non-small cell lung cancer (NSCLC) patients initiating treatment with third generation ALK inhibitor therapy lorlatinib (Press release, EORTC, OCT 29, 2019, View Source [SID1234549947]).

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Although ALK positive NSCLC cancer patients are known to respond well to ALK inhibition therapies, such as lorlatinib, this has been limited in time by the emergence of drug resistance. Furthermore, the impact of acquired resistance on response to sequential therapies is unknown. The study has been designed to better understand resistance mechanisms and to analyze the correlation between ALK resistance mutational profile and response to lorlatinib.

Inivata’s InVisionFirst-Lung ctDNA test will be used initially to provide ‘real-time’ data for the pre-trial selection of patients through the detection of molecular resistance. The liquid biopsy test will also be used to provide data on ALK mutational profile in relation to each patient’s response to lorlatinib treatment at the point of disease progression and throughout the course of the study for those patients in whom new ALK mutations are detected.

Eighty-four patients will be involved in this Phase II study across 30 participating EORTC sites in Belgium, France, Italy, The Netherlands, Norway, Spain and the United Kingdom. EORTC, an independent, non-profit research organization in cancer, is the trial sponsor. The trial is being funded by Pfizer Inc., the marketing authorization holder of lorlatinib.

Clive Morris, Chief Executive Officer at Inivata, said: "This pharmaceutical company-backed collaboration highlights the value of our InVision platform in providing rapid and repeatable genomic profiling to enable new analyses of disease and benefit patient treatment. EORTC is a highly regarded leader in translation research and we look forward to working with them on this important study."

Dr Denis Lacombe, EORTC Director General, said: "Understanding the patterns of resistance and relapse is one of the most burning challenges in oncology. EORTC’s scientific strategy, being primarily patient centered, has developed, over the years, a specific focus on programs which address the entire course of the disease taking forward the challenges that patients face at recurrence. We are, therefore, particularly excited with this partnership which brings together the capacity of our organization and new technologies to address the applicability of liquid biopsy for longitudinal studies on this critical question. Better understanding of resistance will not only provide insight on how to design the next generation of treatment, but could also potentially suggest combination treatment to prevent the development of resistance."

"I would also like to add that this trial protocol was developed in the Methods in Clinical Research workshop (MCCR). This is a workshop to educate early career investigators on how to develop good clinical trial designs and we are delighted that we have been able to implement this protocol."

InVisionFirst-Lung is a ctDNA next generation sequencing liquid biopsy capable of testing 36 genes, including ALK, relevant to the care of patients with advanced NSCLC. The test is available world-wide for both commercial and research use. In the US, InVisionFirst-Lung is covered for Medicare patients with advanced (Stage IIIB/IV) NSCLC who meet specific clinical criteria.

On October 29, 2019 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 initiation of the Phase 2 PROCLAIM (Probody Clinical Assessment In Man) CX-072-002 program evaluating the anti-PD-L1 Probody CX-072, in combination with the anti-CTLA-4 antibody, YERVOY (ipilimumab), in patients with relapsed or refractory melanoma (Press release, CytomX Therapeutics, OCT 29, 2019, View Source [SID1234549966]).

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"The initiation of this first Phase 2 study for CX-072 marks the ongoing advancement of our innovative pipeline of Probody therapeutics and reflects our vision for this novel checkpoint inhibitor to become a differentiated centerpiece of combination therapies in multiple cancer types," said Sean McCarthy, D.Phil., president, chief executive officer and chairman of CytomX Therapeutics.

"Patients whose melanoma has progressed despite prior treatment with checkpoint inhibition remain a significant unmet medical need. This exciting study leverages our unique technology platform to enable a more powerful combination therapy directed against the two best validated pathways in immuno-oncology and could represent a significant advance in outcomes for these patients who have few treatment options," said Amy Peterson, M.D., chief development officer of CytomX Therapeutics.

About the PROCLAIM-CX-072-002 Ipilimumab Combination Study

PROCLAIM-CX-072-002 is an open-label, multi-center Phase 2 clinical study (NCT03993379) that allows for the testing of CX-072 in combination with ipilimumab in patients with unresectable or metastatic melanoma whose disease has progressed or relapsed following treatment with a PD-1/PD-L1 immune checkpoint inhibitor. This study will assess the efficacy and tolerability of a fixed dose of 800 mg of CX-072 every three weeks in combination with ipilimumab at the full labelled combination dose and schedule of 3 mg/kg every three weeks for four cycles. CX-072 therapy will be continued once every two weeks after the completion of the combination phase until disease progression. The primary objective is overall response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with secondary objectives evaluating the safety and tolerability of CX-072. The cohort utilizes a Simon 2 Stage design with approximately 40 patients being enrolled into Stage 1 with additional patients being enrolled into Stage 2, pending the outcome of Stage 1. CytomX anticipates initial data from Stage 1 in 2020.

Additional information on this trial is available at ClinicalTrials.gov using the identifier NCT03993379.

Unmet Need in Relapsed Refractory Melanoma

Melanoma is a life-threatening form of skin cancer. The incidence of melanoma has been increasing over the last 40 years, with about 150K newly diagnosed patients across major markets in 2018. In the unresectable/metastatic setting, approximately 60% of melanoma patients will receive immune checkpoint blockade (~35% of BRAF+ patients and ~75% of BRAF WT) yet ~85% of those patients will progress. For patients with unresectable/metastatic melanoma who progress after PD-1/L1 therapy, there are limited treatment options available.

Updated Top-Line Results from the Phase 1 PROCLAIM-CX-072-001 Ipilimumab Combination Study

This open-label, dose-finding study evaluated CX-072 in combination with ipilimumab in patients with advanced solid tumors. Preliminary data from this trial was first presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting and enrollment is complete. Updated data, as of an October 2019 snapshot, showed that among 27 evaluable patients who received ipilimumab (3, 6 or 10 mg/kg) combined with CX-072 (0.3, 1, 3 or 10 mg/kg), the disease control rate (stable disease or better) was 37%. Five patients achieved confirmed objective responses by RECIST v1.1 including one complete response, for an ORR of 19% in these heavily pretreated patients. The median duration of response was 14.6 months (1.9 – 21.2 months) with 4 of the 5 responders still on treatment as of the latest data snapshot.

The recommended combination dose for further investigation is 3 mg/kg of ipilimumab and 10 mg/kg of CX-072 (dose equivalent of 800 mg). This combination was generally well tolerated with no new safety signals observed. Of the 27 patients treated across all doses, Grade 3/4 treatment related adverse events (TRAE) were reported in 9 (33%) patients and Grade 3/4 immune related adverse events (irAEs) were reported in 6 (22%) patients. Of the 20 patients treated with ipilimumab at 3 mg/kg at varying doses of CX-072, Grade 3/4 TRAEs were reported in 5 (25%) patients and Grade 3/4 irAEs were reported in 3 (15%) patients.

The Company is preparing data from the Phase 1 PROCLAIM-CX-072-001 study for publication.

On October 29, 2019 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 that several posters featuring INTASYL will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2019 Annual Meeting, held November 6-10 at the Gaylord National Hotel and Convention Center in National Harbor, MD (Press release, Phio Pharmaceuticals, OCT 29, 2019, View Source [SID1234549982]). Three posters, reflecting internal work and work in collaboration with Iovance Biotherapeutics, Inc. and the Karolinska Institutet, will be highlighting Phio’s proprietary INTASYL technology for "weaponizing" T cells against cancer.

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Presentation Details:

Poster: P149
Date: Friday November 8, 2019
Title: Silencing PD-1 using self-delivering RNAi PH-762 to improve Iovance TIL effector function using Gen 2 manufacturing method
Category: Cellular Therapies
Authors: Inbar Azoulay-Alfaguter, PhD; Michelle R. Abelson, PhD; Krit Ritthipichai, DVM, PhD; Kenneth D’Arigo; Florangel Hilton; Marcus Machin, BS; Dingxue Yan; James Cardia; Maria Fardis, PhD, MBA; Cecile Chartier

Poster: P222
Date: Saturday November 9, 2019
Title: Modulating BRD4 in T cells using self-delivery RNAi to improve adoptive cell therapy of cancer
Category: Cellular Therapies
Authors: Jeroen Melief, PhD; Laura L. Van Leeuwe Kirsch, BSc; Esmeralda Hemme; John A. Barrett, PhD; Simon P. Fricker, PhD; Gerrit Dispersyn, PhD; Rolf Kiessling, MD, PhD

Poster: P760
Date: Saturday November 9, 2019
Title: Local modulation of T cell PD-1 using self-delivering RNAi as a potential immunotherapeutic
Category: Novel Single-Agent Immunotherapies
Authors: John A. Barrett, PhD; James Cardia; Melissa Maxwell; Mani D. Kadiyala, M.S.; Dingxue Yan, PhD; Winnie Tam; Simon P. Fricker, PhD; Gerrit Dispersyn, PhD

On October 29, 2019 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported a corporate update and reported financial results for the third quarter ending September 30, 2019 (Press release, PTC Therapeutics, OCT 29, 2019, View Source [SID1234549998]).

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"We are following through on our commitment to build an innovative, diversified rare disorders company," said Stuart Peltz, Ph.D., CEO of PTC Therapeutics. "This quarter, we completed a successful financing to continue to drive our internal programs while continuing to evaluate select external opportunities. This most recent financing has put us in a position to execute on our strategic vision of reaching over $1.5B in revenue by 2023."

Corporate Highlights:

Tegsedi (inotersen) received approval from the Brazilian health regulatory authority (ANVISA) for the treatment of stage 1 or 2 polyneuropathy in adult patients with hereditary transthyretin amyloidosis (hATTR), to delay disease progression and improve quality of life. This approval will allow PTC to initiate the launch in Brazil with the only hATTR indication globally to include improvements in quality of life.
PTC acquired assets from BioElectron Technology Corporation that are focused on inflammatory and central nervous system (CNS) disorders. The lead program is pivotal trial ready for CNS disorders with substantial unmet need and significant commercial opportunity that are complementary to PTC’s existing pipeline.
Advancing CNS Gene Therapy Portfolio & Infrastructure:

PTC has entered into a strategic collaboration with Aldevron to support GMP plasmid manufacturing for the gene therapy portfolio.
As previously disclosed, PTC is on track to submit a BLA with the FDA in late 2019 followed by an MAA in Europe for the AADC deficiency gene therapy program. This will be followed by an anticipated commercial launch in 2020.
Data presented in October at the Child Neurology Society meeting demonstrated that patients receiving PTC-AADC had sustained motor, cognitive, and language milestones representing up to five years of follow up post-treatment.
The Friedreich ataxia program continues to advance with an IND submission now expected in mid-2020.
PTC has signed a long-term lease agreement securing a state-of-the-art biologics facility located in Hopewell, N.J. to support the research and operations of multiple gene therapy programs.
Updates for Small Molecule Splicing Platform:

Data from pivotal FIREFISH and SUNFISH part 1 studies were presented at the World Muscle Society Congress in October, demonstrating continued clinical benefit with risdiplam in Type 1, 2, and 3 SMA patients.
In part 1 of FIREFISH, babies with Type 1 SMA continue to achieve motor milestones including at least one patient now standing and two patients starting to walk.
Risdiplam continues to be well tolerated at all doses across studies and there have been no drug related safety findings leading to withdrawal.
Part 2 SUNFISH data is expected by the end of the year followed by part 2 FIREFISH data in early 2020.
Planned NDA filing with the FDA is on track for the second half of this year with the intention to support a broad label to treat SMA Types 1, 2, & 3 patients. Filing of the MAA in the EU is expected to occur in the first half of 2020.
Based on initial feedback from the FDA on the complexity of a clinical pathway for the small population of patients, PTC has decided to discontinue the Familial Dysautonomia oral splicing program.
PTC continues to prioritize our Huntington’s program, which is scaling up with safety and toxicology work and is expected to enter the clinic in 2020.
PTC Full Year 2019 Guidance:

PTC anticipates DMD franchise net product revenues for the full year 2019 to remain between $285 and $305 million.
PTC anticipates GAAP R&D and SG&A expense for the full year 2019 to be between $420 and $430 million.
PTC anticipates Non-GAAP R&D and SG&A expense for the full year 2019 to be between $380 and $390 million, an increase from $360 and $370 million, excluding estimated non-cash, stock-based compensation expense of approximately $40 million, an increase from $35 million. This increase in operating expense is primarily due to the acceleration of activities in our core programs, including research and gene therapy manufacturing.
Third Quarter 2019 Financial Highlights:

Total revenues were $71.4 million for the third quarter of 2019, compared to $53.6 million for the third quarter of 2018.
Translarna net product revenues were $48.3 million for the third quarter of 2019, compared to $30.4 million for the third quarter of 2018. These results reflect the expanded commercialization of Translarna.
Emflaza net product revenues were $22.9 million for the third quarter of 2019, compared to $22.6 million for the third quarter of 2018. These results reflect an increase in the utilization of Medicaid which changed our gross to net assumptions and includes the impact of transitioning to a new specialty pharmacy distributor.
GAAP R&D expenses were $63.1 million for the third quarter of 2019, compared to $54.4 million for the third quarter of 2018. The increase in R&D expenses reflects costs associated with advancing the gene therapy platform and increased investment in research programs as well as advancement of the clinical pipeline.
Non-GAAP R&D expenses were $58.1 million for the third quarter of 2019, excluding $5.0 million in non-cash, stock-based compensation expense, compared to $49.9 million for the third quarter of 2018, excluding $4.4 million in non-cash, stock-based compensation expense.
GAAP SG&A expenses were $49.3 million for the third quarter of 2019, compared to $38.4 million for the third quarter of 2018. The increase in SG&A expenses was primarily due to continued investment in support of our commercial activities.
Non-GAAP SG&A expenses were $43.8 million for the third quarter of 2019, excluding $5.5 million in non-cash, stock-based compensation expense, compared to $33.9 million for the third quarter of 2018, excluding $4.5 million in non-cash, stock-based compensation expense.
Change in the fair value of deferred and contingent consideration was $9.5 million for the third quarter of 2019. The change in fair value of deferred and contingent consideration is related to the fair valuation of potential future consideration to be paid to former equity holders of Agilis Biotherapeutics, Inc. (Agilis) in connection with PTC’s acquisition of Agilis, which closed in August 2018.
Net loss was $60.0 million for the third quarter of 2019, compared to net loss of $51.0 million for the third quarter of 2018.
Cash, cash equivalents, and marketable securities were $708.6 million at September 30, 2019, compared to $227.6 million at December 31, 2018. We completed a financing that amounted to $287.5 million in convertible bonds and $100.0 million in equity for a total consideration of $387.5 million, resulting in net offering proceeds of $376.3 million.
Shares issued and outstanding as of September 30, 2019 were 61,578,992.
Upcoming investor conferences
Credit Suisse 28th Annual Healthcare Conference, November 12th 2:25 pm MT.

Non-GAAP Financial Measures:
In this press release, the financial results and financial guidance of PTC are provided in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, the non-GAAP financial measures exclude non-cash, stock-based compensation expense. These non-GAAP financial measures are provided as a complement to financial measures reported in GAAP because management uses these non-GAAP financial measures when assessing and identifying operational trends. In management’s opinion, these non-GAAP financial measures are useful to investors and other users of PTC’s financial statements by providing greater transparency into the historical and projected operating performance of PTC and the company’s future outlook. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. Quantitative reconciliations of the non-GAAP financial measures to their respective closest equivalent GAAP financial measures are included in the table below.

Today’s Conference Call and Webcast Reminder:
Today’s conference call will take place at 4:30 pm ET and can be access by dialing (877) 303-9216 (domestic) or (973) 935-8152 (international) five minutes prior to the start of the call and providing the passcode 9224968. A live, listen-only webcast of the conference call can be accessed on the investor relations section of the PTC website at www.ptcbio.com. The accompanying slide presentation will be posted on the investor relations section of the PTC website. A webcast replay of the call will be available approximately two hours after completion of the call and will be archived on the company’s website for two weeks.

On October 29, 2019 Evelo Biosciences (NASDAQ:EVLO), a clinical stage biotechnology company developing a new modality of orally delivered, systemically acting biologics, reported that it will host a conference call and live webcast at 8:30 A.M. ET on Tuesday, November 5, 2019 to report its third quarter financial results and discuss recent business updates (Press release, Evelo Biosciences, OCT 29, 2019, View Source [SID1234550234]).

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To access the live conference call, please dial 866-795-3242 (domestic) or 409-937-8909 (international) and refer to conference ID 7788384. A live webcast of the event will also be available under "News and Events" in the Investors section of Evelo’s website at View Source The archived webcast will be available on Evelo’s website approximately two hours after the completion of the event and will be available for 30 days following the call.