On May 29, 2020 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, in collaboration with development partner Servier, an independent international pharmaceutical company, reported positive initial results from Allogene’s dose escalation Phase 1 ALPHA study of ALLO-501 in relapsed/refractory non-Hodgkin lymphoma (NHL) (Press release, Allogene, MAY 29, 2020, View Source [SID1234558697]). Data were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting. This study utilizes ALLO-647, Allogene’s anti-CD52 monoclonal antibody (mAb), as a part of its differentiated lymphodepletion regimen.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are very pleased with these initial Phase 1 results, which indicated that ALLO-501 and ALLO-647 were well tolerated and produced complete responses in patients with advanced NHL," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "Based on these results, we believe we are on the right trajectory to make AlloCAR T therapy a reality for patients."

"Allogeneic CAR T therapies provide an off-the-shelf option that may make cellular therapies available to more patients," said Sattva S. Neelapu, M.D., Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. "While longer follow-up is required, the response to ALLO-501 appears promising with 75% of patients remaining in response. Together with the positive safety profile, these data suggest that ALLO-501 has the potential to be an effective option if confirmed in future studies."

As of the May 2020 data cutoff, 23 patients were enrolled and 22 patients received ALLO-501. One patient was removed from the study prior to lymphodepletion due to acute renal failure from urinary obstruction. The median time from enrollment to the start of therapy was five days.

For the efficacy analysis, 19 out of 22 patients reached at least one month assessment as of the May 2020 data cutoff. Responses were observed across all cell doses and tumor histologies (diffuse large B-cell lymphoma and follicular lymphoma) with an overall response rate (ORR) of 63% and complete response (CR) rate of 37%. Higher dose ALLO-647 was associated with a higher CR rate of 50%, deeper lymphodepletion and delayed host T cell recovery. With a median follow-up of 3.8 months, nine of the 12 responding patients (75%) remain in response as of the data cutoff.

Cell Dose
and LD
regimen 39mg ALLO-647 90mg ALLO-647 All Patients
(N=19)
(95% CI)
40 x 106
CAR+ cells
(N=4) 120 x 106
CAR+ cells
(N=4) 360 x 106
CAR+ cells
(N=3) All 39mg
ALLO-647
(N=11) 120 x 106
CAR+ cells
(N=6) 360 x 106
CAR+ cells
(N=2) All 90mg
ALLO-647
(N=8)
ORR, n (%) 3 (75%) 3 (75%) 1 (33%) 7 (64%) 4 (67%) 1(50%) 5 (63%) 12/19 (63%)
(38%, 84%)
CR, n (%) 1 (25%) 1 (25%) 1 (33%) 3 (27%) 4 (67%) 0 (0%) 4 (50%) 7/19 (37%)
(16%, 62%)
One of the ongoing responders is a patient with an initial partial response (PR) who progressed by month two. This patient achieved a CR after re-treatment with the same dose of ALLO-501 and higher dose (90mg) ALLO-647. This patient is reflected as a PR in the table above and not as a CR.

Included in the overall efficacy analysis are three patients who were refractory to prior autologous CAR T therapy (the best response of progressive disease or disease progression within three months). These patients were also refractory to AlloCAR T therapy. In CAR T naïve patients, the ORR was 75% and the CR rate was 44%.

All Cell Doses +
39mg ALLO-647
(N=10) 120 x 106 and 360 x 106 CAR+ cells +
90mg ALLO-647
(N=6) All CAR T Naïve Patients
(N=16)
ORR, n (%) 7 (70%) 5 (83%) 12/16 (75%)
(48%, 93%)
CR, n (%) 3 (30%) 4 (67%) 7/16 (44%)
(20%, 70%)
No dose limiting toxicities, graft-vs-host disease, or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed.

Adverse Events of Interest Grade 1
N (%) Grade 2
N (%) Grade 3
N (%) Grade 4
N (%) Grade 5
N (%)
Cytokine Release Syndrome 2 (9%) 4 (18%) 1 (5%) - -
ICANS - - - - -
Graft-versus-Host Disease - - - - -
Infection 5 (23%) 4 (18%) 2 (9%) - -
Infusion Reaction 1 (5%) 9 (41%) 1 (5%) - -
Neutropenia - 1 (5%) 7 (32%) 7 (32%) -
Cytokine release syndrome occurred in 32% of the patients, was mainly mild to moderate in severity, manageable with standard recommendations, and all events resolved within a maximum of seven days. Patients treated with 90mg ALLO-647 did not experience an increase in infection as compared to those treated with 39mg ALLO-647.

Four patients (18%) experienced serious adverse events (SAE). One patient had Grade 2 pyrexia and Grade 2 cytomegalovirus (CMV) reactivation which resolved in two days and six days, respectively. One patient had Grade 3 rotavirus infection and Grade 3 hypokalemia which resolved in 15 days and two days, respectively. One patient had Grade 3 febrile neutropenia and Grade 3 hypotension which each resolved in two days. One patient had a Grade 3 upper GI hemorrhage which resolved in one day and Grade 3 CMV reactivation which resolved in 25 days.

Adverse events were observed across all dose levels of ALLO-501 and ALLO-647. SAEs were observed at ALLO-501 cell dose level 40 x 106 and 120 x 106 and at both dose levels of ALLO-647.

"We are pleased to see the progress made by Allogene in the ALPHA trial and the positive initial data for ALLO-501," said Olivier Laureau, President of Servier. "Our teams are proud to play a role in helping to develop innovative therapies for patients in need."

Allogene is the sponsor of the Phase 1 ALPHA trial which is designed to assess the safety and tolerability at increasing dose levels of ALLO-501 and ALLO-647 in the most common NHL subtypes of relapsed/refractory diffuse large B-cell lymphoma or follicular lymphoma.

ALLO-501A is a next generation anti-CD19 AlloCAR T devoid of the rituximab recognition domains found in ALLO-501. This could allow for use in a broader patient population, including those NHL patients with recent rituximab exposure. ALLO-501A is intended for Phase 2 development and enrollment has been initiated in the Phase 1 portion of the ALPHA2 trial of ALLO-501A.

Webinar
Please register for the webinar on the Company’s website at www.allogene.com under the Investors tab in the News and Events section (View Source) or by clicking the following link directly.

The webinar will be available as a live event only and the materials presented will be available on the Allogene website prior to the start of the event.

About ALLO-501 (Allogene Sponsored)
ALLO-501 is an anti-CD19 allogeneic CAR T (AlloCAR T) therapy being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. ALLO-501 uses Cellectis technologies. Servier grants to Allogene exclusive rights to ALLO-501 in the U.S. while Servier retains exclusive rights for all other countries.

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").

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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).

On May 29, 2020 Suzhou Kintor Pharma reported that it has completed a $240 million IPO on the Hong Kong Exchange (Press release, Suzhou Kintor Pharmaceuticals, MAY 29, 2020, View Source [SID1234558695]). Kintor is focused on androgen receptor related diseases including prostate cancer, breast cancer, liver cancer and alopecia. Its pipeline includes novel small molecule drugs, biologics and combination therapies. Kintor expects its lead drug, a prostate cancer candidate known as proxalutamide, will be approved for China commercialization later this year. The IPO was more than 500 times oversubscribed, and Kintor’s shares rose slightly in initial trading

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On May 29, 2020 Heat Biologics, Inc. ("Heat") (NASDAQ:HTBX), a clinical-stage biopharmaceutical company focused on developing first-in-class therapies to modulate the immune system, including multiple oncology product candidates and a novel COVID-19 vaccine, reported its latest data at the ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, Heat Biologics, MAY 29, 2020, View Source [SID1234558694]). The poster presentation can be viewed on the ASCO (Free ASCO Whitepaper) meeting website at: View Source and on Heat Biologics’ website at: View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

HS-110 is an "off-the-shelf" allogeneic cell-based therapy designed to activate patients’ immune system against multiple cancer testis antigens (CTAs) to elicit a diverse and robust T-cell attack against tumor cells. A Phase 2 trial of HS-110 in combination with Bristol-Myers Squibb’s (BMS) Opdivo (nivolumab) for multiple treatment settings in advanced non-small cell lung cancer (NSCLC) is ongoing, with enrollment of this trial completed in July 2019.

This data demonstrated that significant survival benefit was observed in a cohort of previously treated, checkpoint inhibitor (CPI) naïve patients with advanced NSCLC; with a median overall survival (mOS) of 28.7 months for the intent-to-treat (ITT) patients (N = 47). This data compares favorably with published data of Checkmate 057, which reported a mOS of 12.2 months in patients who received nivolumab as single agent in a similar treatment setting. Notably, a statistically significant survival benefit with mOS of 42.1 months was observed in patients with injection site reaction (p = 0.0001). Exploratory biomarker analyses showed that overlapping CTA expression in patients’ tumors at baseline with HS-110, as well as the expression of a specific CTA were both associated with statistically significant improved overall survival (p = 0.028 and 0.008, respectively).

"Our exploratory biomarker analysis solidly establishes additional clinical evidence for the HS-110 mechanism of action," said Jeff Hutchins, Chief Scientific and Operating Officer of Heat. "This extended mOS also suggests that HS-110 treatment in combination with a CPI should be considered for any solid tumor type with sufficient CTA overlap with HS-110."

This study has completed enrollment, and 21 of the 47 patients enrolled (45%) are still alive as of this data cut. HS-110 now has a positive safety profile in over 200 patients, and combination of HS-110 and nivolumab appears to be safe and well-tolerated.

"This updated data demonstrates the potential utility of HS-110 in combination with a checkpoint inhibitor as a frontline treatment for NSCLC", said Jeff Wolf, Chief Executive Officer of Heat. "Heat is planning an end-of-phase 2 meeting with the FDA to discuss registration trial design."

On May 29, 2020 Incyte (Nasdaq:INCY) reported that data from the interim analysis of the Phase 2 OPTIC (Optimizing Ponatinib Treatment In CML) trial, which was sponsored by Takeda and co-funded by Incyte, will be presented during an oral session at the upcoming 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Meeting (ASCO20; May 29 – May 31) (Abstract #7502)1; and at the virtual 25thCongress of the European Hematology Association (EHA) (Free EHA Whitepaper) (EHA25; June 11 – 14) (Abstract #S172)2 (Press release, Incyte, MAY 29, 2020, View Source [SID1234558693]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The OPTIC trial is an ongoing randomized, open-label study prospectively evaluating response-based dosing regimens of Iclusig (ponatinib) over a range of three starting doses (45 mg, 30 mg, 15 mg) with the aim of optimizing its efficacy and safety in patients with chronic-phase chronic myeloid leukemia (CP-CML), who are resistant or intolerant to prior tyrosine kinase inhibitor (TKI) therapy. With a median follow up of approximately 21 months, data from the interim analysis of the OPTIC trial show that the optimal benefit-risk profile for Iclusig in patients with CP-CML is achieved with a daily starting dose of 45 mg followed by a dose reduction to 15 mg upon achieving ≤1% BCR-ABL1. This dosing regimen resulted in an adjudicated arterial occlusive event (AOE) rate of 5.3%.

"As a physician, my focus is on treating CP-CML patients in a manner that will provide the best possible outcome by achieving desirable efficacy, while maintaining a manageable safety profile," said Dr. Gianantonio Rosti, M.D., Institute of Haematology and Oncology, St Orsola University Hospital, Bologne. "I believe that patient selection, good management of comorbidities, close monitoring and appropriate dose adjustments are key factors in the management of CP-CML. I am encouraged by these data on the benefit-risk profile that is emerging from the interim OPTIC data of the Iclusig regimen starting at 45 mg, followed by a dose reduction to 15 mg."

"The interim data from OPTIC provide important additional context around the safety profile of Iclusig in appropriate patients with CP-CML." said Luca Marini, M.D., Regional VP, Head of European Medical Affairs, Incyte. "We believe that they may offer additional guidance to healthcare providers on how to optimize treatment with the goal of maintaining efficacy while reducing the risk of arterial occlusive events."

Key findings from the OPTIC interim analysis (IA; cutoff date of July 2019) include:

With median follow-up time of approximately 21 months, 77% (n/N=216/282) of patients in the OPTIC trial were evaluable for the primary endpoint.
The OPTIC IA shows benefit of ponatinib in all three starting doses in a largely resistant population where the majority of patients (>60%) demonstrated less than a complete hematologic response (CHR) to immediate prior therapy.
The maximum rates of ≤1% BCR-ABL1IS at 12 months were achieved in the 45 mg/day starting dose cohort (38.7%), and responses were maintained with the dose reduction to 15 mg/day.
With the protocol-mandated dose reduction for response in the higher dose cohorts, 75% patients in 45 mg cohort and 88% patients in 30 mg cohort were able to maintain ≤1% BCR-ABL1IS response for as long as up to two years.
Safety data as of the IA cutoff date include:
Among all patients (N=282), the most common treatment-emergent adverse events (TEAEs) of any grade (occurring in ≥10% of all patients) were thrombocytopenia (39.4%), neutropenia (25.2%), hypertension (24.1%), anemia (17.4%), headache (17.0%), increased lipase (16.0%), arthralgia (14.2%), constipation (12.4%), platelet count decrease (10.6%) and ALT increase (10.3%).
There was a dose-dependent trend in arterial occlusive event (AOE) rates:
Pre-adjudicated AOEs were reported in (45 mg, 30 mg, 15 mg/day starting dose cohorts) 8.5% (n/N = 8/94), 4.3% (n/N = 4/94), and 2.1% (n/N = 2/94).
Prospective adjudication of AOEs by independent experts resulted in (45 mg, 30 mg, 15 mg/day starting dose cohorts) 5.3% (n/N = 5/94), 4.3% (n/N = 4/94), and 1.1% (n/N = 1/94).
At the IA, there were no AOE-related deaths reported.
The complete primary analysis of the OPTIC trial will be conducted after all patients have at least 12 months of follow-up and will be presented at a later date.
Incyte has an exclusive license from Takeda Pharmaceuticals International AG to commercialize Iclusig in the European Union and 29 other countries, including Switzerland, UK, Norway, Turkey, Israel and Russia. Iclusig is marketed by Takeda Pharmaceuticals International AG in the U.S.

About the OPTIC Trial

OPTIC (Optimizing Ponatinib Treatment In CML) is a randomized, dose-ranging Phase 2 trial designed to evaluate three starting doses (15 mg, 30 mg, 45 mg) of Iclusig (ponatinib) in patients with resistant chronic-phase chronic myeloid leukemia (CP-CML) or who had documented history of presence of T315I mutation after receiving any number of prior tyrosine kinase inhibitors (TKIs). Dose reduction at response occurred per study protocol. The trial is expected to inform the optimal use of Iclusig in these patients. The primary endpoint of the trial is achieving ≤1% BCR-ABL1 at 12 months. Approximately 283 patients were enrolled at clinical sites around the world. Dose reduction at response occurred per study protocol.

For more information about the OPTIC study, please visit: View Source

About CML and Ph+ ALL

CML – a rare malignancy – is one of four main types of leukemia; it is a result of a genetic mutation that takes place in early, immature versions of myeloid cells, which form red blood cells, platelets and most types of white blood cells. Subsequently, an abnormal gene called BCR-ABL1 forms, turning the damaged cell into a CML cell. CML typically progresses slowly, but it can change into a fast-growing acute leukemia that is hard to treat.

Ph+ ALL is a rare form of ALL that accounts for one quarter of adult ALL cases. and is characterized by the presence of an abnormal gene, known as the Philadelphia chromosome. In patients who are Philadelphia chromosome positive (Ph+), an abnormal chromosome is formed when pieces of chromosomes 9 and 22 switch with each other. This forms a longer chromosome 9 and a shorter chromosome 22, which leads to the development of BCR-ABL1 and is associated with Ph+ ALL.

About Iclusig (ponatinib) Tablets

Iclusig targets not only native BCR-ABL but also its isoforms that carry mutations that confer resistance to treatment, including the T315I mutation, which has been associated with resistance to other approved TKIs.

Iclusig is approved in the U.S., EU, UK, Australia, Switzerland, Israel and Canada.

In the EU, Iclusig is approved for the treatment of adult patients with chronic phase, accelerated phase or blast phase chronic myeloid leukemia (CML) who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or the treatment of adult patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation.