On November 6, 2018 Sorrento Therapeutics, Inc. (NASDAQ: SRNE) ("Sorrento") reported the release of data from a phase 1b clinical trial administering anti-CEA CAR-T by utilizing a unique Pressure-Enabled Drug Delivery (PEDD) manufactured by TriSalus Life Sciences (Press release, Sorrento Therapeutics, NOV 6, 2018, View Source [SID1234532249]). The preliminary data for the Hepatic Immunotherapy for Metastases (HITM-SURE) clinical trial results will be presented in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, being held November 7-11 in Washington, DC.

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Five patients, four pancreatic and one colorectal, with carcinoembryonic antigen–positive (CEA+), unresectable stage IV adenocarcinoma with liver metastases, who had failed one or more lines of systemic chemotherapy, each received three hepatic artery infusions of Sorrento autologous anti-CEA CAR-T cells using the Hepatic Immunotherapy for Metastases (HITM) method. The immunotherapy was delivered by means of PEDD technology, which overpowers the high pressure within solid tumors that limits the reach and efficacy of therapeutic agents.

Two out of the four pancreatic cancer patients had no viable liver metastases by PET scan after treatment. After 12 months, one patient with stage IV pancreatic carcinoma still showed no evidence of liver metastases on PET imaging, and his primary pancreatic tumor was well-controlled. A second patient with stage IV pancreatic cancer also had no evidence of liver metastases six weeks after CAR-T/PEDD infusions. Median overall survival (OS) post-treatment is 8.3 months and the mean OS is 9.8 months to date. No patient suffered any severe adverse event related to the CAR-T infusions.

"PEDD significantly increased CAR-T, more than five-fold, within liver metastases when compared with low-pressure microcatheters, and serum CEA levels declined on-study in all subjects," said Steven Katz, MD, director of the Office of Therapeutic Development at the Roger Williams Medical Center, and the principal investigator of the trial. "These early results suggest we may be able to achieve a therapeutic dose in solid tumors and avoid the severely limiting systemic side effects, such as neurotoxicity and cytokine release syndrome, that are prevalent with conventional systemic CAR-T administration methods. Furthermore, our delivery approach limits the number of circulating CAR-T cells compared to systemic delivery, which has the potential to improve the safety profile of CAR-T therapies for solid tumors in several critical organs."

"With our CD38 and CEA CAR-T programs, we are addressing the challenges of treating both liquid and solid tumors," stated Henry Ji, PhD, President and CEO. "We are scheduled to discuss with the FDA the continued development of this program towards Licensure."

On November 6, 2018 Exelixis, Inc. (NASDAQ: EXEL) reported that Michael M. Morrissey, Ph.D., the company’s President and Chief Executive Officer, will provide an overview of the company at the Stifel 2018 Healthcare Conference taking place November 13-14 in New York, NY (Press release, Exelixis, NOV 6, 2018, View Source;p=RssLanding&cat=news&id=2375655 [SID1234530765]). The Exelixis presentation is scheduled for 10:15 AM EST / 7:15 AM PST on Tuesday, November 13, 2018.

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To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 14 days.

On November 6, 2018 PharmaCyte Biotech, Inc. (OTCQB: PMCB), a clinical stage biotechnology company focused on developing targeted cellular therapies for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that it has selected Medpace, Inc. as the Contract Research Organization (CRO) to conduct PharmaCyte’s clinical trial in locally advanced, non-metastatic, inoperable pancreatic cancer (LAPC) (Press release, PharmaCyte Biotech, NOV 6, 2018, View Source [SID1234530787]).

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PharmaCyte Biotech’s Chief Executive Officer, Kenneth L. Waggoner, commented on PharmaCyte’s selection saying, "Our Clinical Trial Leadership Team (CTLT) worked diligently to identify and select the right CRO to conduct our clinical trial in LAPC. Medpace is an established and highly regarded full-service CRO with expertise in numerous therapeutic areas focused on supporting the biotech sector. It is a scientifically-driven organization with a dedicated in-house study team supported by outstanding medical experts to lead the way. Medpace has an extensive portfolio of successfully completed clinical trials, including those involving pancreatic cancer.

"Although we considered several outstanding CRO candidates, we felt that Medpace was the ideal choice to be our CRO as the team at Medpace provides experience and a range of services to conduct virtually every aspect of our Phase 2b clinical trial in LAPC. In 2018, Medpace was ranked among the top 10 CROs in the world. During the selection process, it was easy to see why Medpace is so highly ranked."

Selection of the CRO for PharmaCyte’s clinical trial in LAPC was performed by PharmaCyte’s CTLT led by Dr. Linda Sher, PharmaCyte’s Chief Medical Officer, and Dr. Manuel Hidalgo who will serve as Principal Investigator for the trial. The selection process was both laborious and time-consuming. Initially, 10 CRO candidates were identified. After an initial screening, this number was reduced to 8. Thereafter, careful examination and scrutiny of the qualifications and references of the 8 candidates led to the selection of the top 4 candidates.

Each of the 4 remaining candidates was then sent a Request for Proposal (RFP) to conduct the trial. After receiving the RFP proposals, interviews of the 4 remaining CROs were conducted by telephone. Finally, an in-depth analysis by PharmaCyte’s CTLT was conducted, which reduced the number of CRO candidates to the top 2. The top 2 CRO candidates were interviewed in person by members from the CTLT. Both candidates were outstanding and impressive.

The decision to select Medpace was unanimous among the members of the CTLT evaluation team. Although Medpace is a multidisciplinary full-service CRO, its largest therapeutic area of focus is in oncology, and it is very experienced in conducting pancreatic cancer clinical trials.

"Medpace is pleased to have been chosen by PharmaCyte Biotech to conduct its Phase 2b study in LAPC," said Lyon Gleich, MD, FACS, Vice President, Medical Department, Oncology at Medpace. "Our team has the appropriate therapeutic experience in conducting clinical trials in pancreatic cancer. We look forward to partnering with PharmaCyte Biotech and utilizing our knowledge and experience in oncology clinical trials to conduct this important study."

On November 6, 2018 Principia Biopharma Inc. (Nasdaq: PRNB), a clinical-stage biopharmaceutical company dedicated to bringing transformative oral therapies to patients with significant unmet medical needs in immunology and oncology, reported financial results for the third quarter ended September 30, 2018 (Press release, Principia Biopharma, NOV 6, 2018, View Source [SID1234530827]).

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"The completion of our IPO with gross proceeds of approximately $122.2 million was the highlight of the third quarter for Principia. In addition, we continued with preparations for our upcoming PRN1008 Phase 3 trial in patients with pemphigus, and we achieved an important milestone in our collaboration with Sanofi for our BTK inhibitor PRN2246," said Martin Babler, Chief Executive Officer of Principia.

Third Quarter Financial Results

For the three months ended September 30, 2018, Principia reported net income of $6.7 million compared to a net loss of $7.1 million for the same period in 2017.

Collaboration revenue was $18.6 million for the three months ended September 30, 2018, compared to $1.5 million for the same period in 2017. The increase was due to the revenue recognition of an upfront payment of $40.0 million received in December 2017, as well as the revenue recognition of milestone payments totaling $15.0 million received in 2018, related to the Company’s collaboration with Sanofi.

Total research and development expenses were $9.2 million for the three months ended September 30, 2018, including stock-based compensation expense of $0.3 million, compared to $6.1 million for the same period in 2017, including stock-based compensation expense of $0.2 million. The increase in total research and development expenses was mainly due to an increase in PRN1008 program costs related to the initiation of an ITP clinical trial in December 2017, certain manufacturing campaigns as well as an increase in employee related expenses.

General and administrative expenses were $2.9 million for the three months ended September 30, 2018, including stock-based compensation expense of $0.4 million, compared to $1.3 million for the same period in 2017, including stock-based compensation expense of $0.1 million. The increase in total general and administrative expenses was primarily attributable to employee related expenses and facility costs.

Cash, cash equivalents, and short-term investments were $188.3 million as of September 30, 2018, compared to $41.1 million as of December 31, 2017. The increase in cash reflects net proceeds of $49.8 million from Principia’s Series C convertible preferred stock financing, and $113.6 million from Principia’s initial public offering (IPO).

On November 6, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported financial results for the third quarter ended September 30, 2018, and provided a business update (Press release, Adaptimmune, NOV 6, 2018, View Source [SID1234530851]).

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"We have now completed the three dose escalation cohorts of the studies with MAGE-A4 and MAGE-A10, our leading wholly owned programs. The Safety Review Committee has agreed that the higher pre-conditioning regimen and cell doses are tolerable and there were no dose limiting toxicities. These studies will now move into the expansion phase, which allows us to treat patients with up to ten billion cells, without a pre-determined stagger across a broad range of tumor types. We have also continued dosing patients in the AFP study with 100 million cells and anticipate escalating to Cohort 2 in early 2019. We expect to report our next clinical data by no later than our first quarter financial results in May 2019," said James Noble, Chief Executive Officer.

Clinical momentum in wholly owned programs

Ongoing MAGE-A10 and MAGE-A4 studies

· There are three ongoing studies with MAGE-A10 and MAGE-A4 SPEAR T-cells

· Two MAGE-A10 studies: one in non-small cell lung cancer (NSCLC) and a triple tumor study in bladder, melanoma, and head & neck cancers

· A MAGE-A4 basket study in NSCLC, bladder, melanoma, synovial sarcoma, myxoid/round cell liposarcoma (MRCLS), head & neck, ovarian, gastric, and esophageal cancers

· All three studies are first-in-human trials utilizing a modified 3+3 design with escalating target doses of 100 million (Cohort 1), 1 billion (Cohort 2), and 5 billion (Cohort 3) transduced SPEAR T-cells to evaluate safety, including dose limiting toxicities (DLTs)

· The preconditioning regimen in the first two cohorts was cyclophosphamide (600mg/m2/day) and fludarabine (30 mg/m2/day) on days -7, -6 and -5, and an extra day of fludarabine was added to the third cohorts and expansion phases, as clinical and translational data indicate that this extra day may be important for optimal T-cell expansion post-infusion

· Following the initial three cohorts, the Safety Review Committee (SRC) meets to decide whether to progress to the expansion phase, which has a target dose of 5 billion cells (range 1.2 to 10B) without pre-determined intervals between patient dosing

· The SRC recommended moving into the expansion phase for the MAGE-A10 triple tumor and MAGE-A4 basket studies

· As in the first two cohorts of these studies, there was no evidence of toxicity related to off-target binding or alloreactivity in the third cohorts at target doses of 5 billion cells

· Most adverse events were consistent with those experienced by cancer patients undergoing chemotherapy or other immunotherapies

ESMO data

· Initial safety data from the first two cohorts of the MAGE-A10 and MAGE-A4 studies were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress (https://bit.ly/2PdB3CR)

· In brief, these data showed:

· Disease progressed for all eight patients treated in the first dose cohorts of the two MAGE-A10 studies (five patients with lung cancer, two with head & neck cancer, and one with melanoma)

· For the three patients treated in Cohort 2 of the MAGE-A10 study (all lung cancer patients), one patient died of pneumonia (unrelated to therapy) and two had stable disease (SD), albeit transient

· Of the six patients treated in Cohorts 1 and 2 of the MAGE-A4 basket study, best response was SD in four patients and progressive disease (PD) in two patients

·One patient in the MAGE-A4 basket study with SD had an overall 27% reduction of target lesions observed at Week 6, and was assessed as PD at the time of the second scan, which took place after the ESMO (Free ESMO Whitepaper) poster cut-off date

· No evidence of toxicity related to off-target binding or alloreactivity at target doses of 100 million or 1 billion cells

· Most adverse events consistent with those experienced by cancer patients undergoing chemotherapy or other immunotherapies

· Transduced cells detectable in peripheral blood at levels consistent with dose

Data from ongoing AFP study

· Dosing in Cohort 1 of AFP study is ongoing

· Anticipate dose escalation to Cohort 2 in early 2019.

NY-ESO data updates to be presented at SITC (Free SITC Whitepaper)

·The NY-ESO program transitioned to GSK in July 2018

·An abstract summarizing NY-ESO SPEAR T-cells in MRCLS was accepted for presentation at SITC (Free SITC Whitepaper), and is available online today

· Data in the abstract state that out of ten MRCLS patients, there were four with partial responses (PRs) and four with SD, as per investigator assessment

· These data will be updated in a poster at SITC (Free SITC Whitepaper)

· Overall, there was evidence of reduction in target lesions in seven patients out of eight evaluable patients

· The data submitted in the abstract included investigator assessments. These assessments showed a best response of four confirmed PR, one unconfirmed PR, and three patients with SD out of eight evaluable patients

· Two of the responses were confirmed before the minimum 28 days required by RECIST v1.1 (22 and 25 days), and the patients subsequently progressed

· Therefore, the response rate by RECIST, which will be presented in the poster, is two confirmed PRs and six patients with SD out of the eight evaluable patients

· Patients in the MRCLS study received the same preconditioning regimen as was used in Cohort 4 of the synovial sarcoma study, and these patients had less durable responses compared to Cohort 1 patients in the synovial sarcoma study, who received a more intense preconditioning regimen

· The most frequent AEs were consistent with those experienced by patients with cancer who are undergoing cytotoxic chemotherapy or other immunotherapies

· A second poster with NY-ESO data will also be presented at SITC (Free SITC Whitepaper) summarizing translational research conducted in the context of the NY-ESO synovial sarcoma study examining serum factors that lead to T-cell expansion with different preconditioning regimens (including the impact of fludarabine), tumor micro-environment analyses pre- and post-infusion, and SPEAR T-cell functionality post-infusion. This abstract is also available online.

Manufacturing

Adaptimmune on its way to becoming a fully integrated cell therapy company

· 2018 has been a successful year for manufacturing with the Navy Yard facility regularly producing target cell doses > 1 billion cells with more than 50% producing > 5 billion cells

· Producing cell doses across multiple solid tumor indications

· Cells have been manufactured for a number of patients who could enter the MAGE-A4 and/or MAGE-A10 expansion phases, once eligible

Other corporate news

Adaptimmune is focused on its next stage of development and in a strong position to deliver success with SPEAR T-cell therapies

· Announced the closing of a registered direct offering of Adaptimmune’s American Depositary Shares ("ADSs") (https://bit.ly/2MZFEIH) with net proceeds of approximately $100 million

· Adaptimmune intends to use the net proceeds from this offering to advance the Company’s wholly owned pipeline of SPEAR T-cell candidates through clinical trials as well as for other general corporate purposes

· Completed transition of NY-ESO IND to GSK and received approximately $26 million in milestone payments

· Funded through to late 2020 with cash and cash equivalents of $153.1 million and total liquidity(1) of $237.7 million

· Held annual Scientific Advisory Board meeting in October with Adaptimmune R&D leaders and external experts in immunology and oncology (bios available here: https://bit.ly/2PvHH4w); focused on optimal employment of NY-ESO learnings in ongoing and future studies as well as strategies for novel target identification

Financial Results for the three and nine month period ended September 30, 2018

· Cash / liquidity position: As of September 30, 2018, Adaptimmune had cash and cash equivalents of $153.1 million and Total Liquidity(1) of $237.7 million.

· Revenue: Revenue for the three and nine months ended September 30, 2018 was $40.8 million and $58.0 million, respectively, compared to $27.2 million and $33.6 million for the same periods of 2017. The revenue in the three and nine months ended September 30, 2018 includes $39.1 million of revenue for the license to NY-ESO, which commenced in September 2018.

· Research and development ("R&D") expenses: R&D expenses for the three and nine months ended September 30, 2018 were $23.5 million and $75.5 million, respectively, compared to $24.0 million and $62.2 million for the same periods of 2017. The R&D expenses in the nine months ended September 30, 2018 has increased compared to the same period in 2017 due to increased clinical trial and related manufacturing activities. R&D expenses in the three months ended September 30, 2018 compared to the same period in 2017 decreased due to the transfer of the NY-ESO program to GSK.

· General and administrative ("G&A") expenses: G&A expenses for the three and nine months ended September 30, 2018 were $10.3 million and $32.8 million, respectively, compared to $8.1 million and $22.3 million for the same periods of 2017. The increase was primarily due to increased personnel costs consistent with the Company’s planned infrastructure growth.

· Other (expense) income, net: Other expense for the three and nine months ended September 30, 2018 was $2.2 million and $10.5 million, respectively, compared to an income of $3.6 million and $7.2 million for the same periods of 2017. Other income primarily comprises unrealized foreign exchange gains, which fluctuate depending on exchange rate movements and the amount of foreign currency assets and liabilities.

· Net income (loss): Net income (loss) attributable to holders of the Company’s ordinary shares for the three and nine months ended September 30, 2018 was an income of $5.2 million and a loss of $59.3 million, respectively, ($0.01 and $(0.10) per ordinary share) compared to a loss of $0.9 million and $42.9 million, respectively, ($(0.00) and $(0.08) per ordinary share) in the same periods of 2017.

(1) Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below.

Financial guidance

The Company believes that its existing cash, cash equivalents and marketable securities will fund the Company’s current operations through to late 2020.

Conference call information

The Company will host a live teleconference and webcast at 8:00 a.m. EST (1:00 p.m. GMT) today. The live webcast of the conference call will be available via the events page of Adaptimmune’s corporate website at www.adaptimmune.com. An archive will be available after the call at the same address. To participate in the live conference call, please dial (833) 652-5917 (U.S.) or +1 (430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (2458438).