On February 27, 2019 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported financial results for the fourth quarter and year ended December 31, 2018 and provided a business update (Press release, Adaptimmune, FEB 27, 2019, View Source [SID1234533726]).
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"2018 was a year of strong delivery across the portfolio with record numbers of patients treated in our clinical trials. We moved through the dose escalation portion of our studies with ADP-A2M4 and ADP-A2M10 and we are now treating patients in the expansion phases for both programs. Our third program, ADP-A2AFP, moved to the second dose cohort at target doses of 1 billion cells. We are very pleased to have observed an acceptable safety profile, thus far, with all three programs, showing no evidence of off-target toxicity or alloreactivity," said James Noble, Chief Executive Officer. "We are now able to devote our resources to these programs following the successful transition of NY-ESO to GSK."
"We made equally impressive progress in manufacturing with our in-house facility going from our first ever dose, at the beginning of 2018, to being able to produce target doses for up to 10 patients per month. In the UK, we started up our vector manufacturing that should begin to produce vector later this year. 2019 promises to be a significant year, with data emerging across our portfolio from May onwards. We look forward to reporting clinical data throughout the year," added James Noble.
Clinical momentum
Initial safety testing is complete in the triple tumor and non-small cell lung cancer (NSCLC) studies with ADP-A2M10, as well as the basket study with ADP-A2M4. All three studies are enrolling and treating patients with up to 10 billion cells in the expansion phases with no pre-determined stagger between dosing required.
In 2018, the Safety Review Committee (SRC) endorsed dose escalation through Cohorts 1, 2, and 3 of these studies, after reviewing safety data from 16 patients treated in the ADP-A2M10 studies and nine patients in the ADP-A2M4 study.
In the hepatocellular carcinoma study with ADP-A2AFP, the SRC endorsed escalation to safety Cohort 2 to treat patients with a target dose of 1 billion cells.
To date, across all four studies, most adverse events have been consistent with those typically experienced by cancer patients undergoing cytotoxic chemotherapy or other cancer immunotherapies with no evidence of alloreactivity or toxicity related to off-target binding.
Building an integrated company
Since the opening of the Navy Yard facility in January 2018, Adaptimmune can now manufacture cells for up to 10 patients per month, and this is scalable to 100 patients per month without significant capital expenditure. Further, an additional 10 patients per month can be treated with cells produced at a third-party vendor HCATs. Both the Navy Yard and HCATs facilities are now able to routinely produce cells to meet target doses across a broad range of solid tumors. This capacity will allow Adaptimmune to service its existing and planned clinical trials.
With respect to vector, Adaptimmune is well supplied as its own vector manufacturing has completed its first engineering run with first production anticipated in 2019, as well as production in place at a third-party vendor. The vendor has already produced vector for ADP-A2M10, ADP-A2M4, ADP-A2AFP, and next generation SPEAR T-cells.
In light of the Company’s increased clinical focus, Rafael Amado assumed the new role of President of R&D last year to bring the clinical and research functions under a single leadership, facilitating alignment and integration of all parts of the R&D structure.
The Company is working with more than 20 active clinical trial sites at leading cancer centers in the US, Canada, and the EU. In Europe, the infrastructure has been tested and has delivered the first doses to patients with additional patients being enrolled in the UK and Spain. Adaptimmune has also reached agreement on an expanded collaboration with MD Anderson Cancer Center (Houston, TX) to further enhance the Company’s translational research capabilities.
While progressing studies with ADP-A2M10, ADP-A2M4, and ADP-A2AFP as well as planning for the next stage of clinical development, including potential registration trials, Adaptimmune continues to progress developing next generation SPEAR T-cells, new targets, other HLAs, and an off-the-shelf product.
Finally, Adaptimmune is funded through to late 2020, based on management’s current estimates, with Total Liquidity(1) of $205 million (including cash and cash equivalents of $68 million) at year-end 2018.
2018 Highlights
Clinical progress with wholly-owned programs:
·ADP-A2M10 (MAGE-A10):
·January 2018: The SRC endorsed escalation to Cohort 2 (1 billion target dose) in the ADP-A2M10 triple tumor and lung studies based on favorable safety data
·ASCO: Poster presented at ASCO (Free ASCO Whitepaper) with initial safety data
·July: SRC endorsed dose escalation to Cohort 3 in the NSCLC and triple tumor studies, and treating patients at target dose of 5 billion cells commenced
·ESMO: Presentation of Cohorts 1 and 2 safety data showing dose proportionate persistence and expansion
·Q4: Escalation to expansion phase allowing for doses up to 10 billion cells with no pre-determined stagger between patients for both studies
·ADP-A2M4 (MAGE-A4) — Basket study:
·ASCO: The SRC endorsed escalation to Cohort 2 based on favorable safety data in Cohort1. Added synovial sarcoma and myxoid/round cell liposarcoma (MRCLS) indications for a total of nine solid tumors in this study
·August: Dose escalation to Cohort 3
(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.
· ESMO (Free ESMO Whitepaper): Presentation of Cohorts 1 and 2 safety data showing dose appropriate persistence and expansion, and early, but transient, evidence of antitumor activity in one ovarian cancer patient
· Q4: Escalation to expansion phase allowing for doses up to 10 billion cells with no pre-determined stagger between patients
·ADP-A2AFP (AFP) – Hepatocellular carcinoma:
· SRC endorsed escalation to Cohort 2 with target doses of 1 billion cells
· Clinical learnings
· AACR (Free AACR Whitepaper) 2018: Presented two posters with ADP-A2M10 and ADP-A2M4 preclinical data
· Q2: Published study in Cancer Discovery indicating that NY-ESO SPEAR T-cells are long-lived, self-renewing, and capable of persistent anti-tumor effects
· SITC (Free SITC Whitepaper): Updated data supporting further understanding of systemic and local immunity following NY-ESO treatment in synovial sarcoma, including the positive impact of a more intense pre-conditioning regimen with respect to SPEAR T-cell expansion and persistence; adjusted to a more intense pre-conditioning regimen in current trials as a result
· Q4: Published paper in Hepatology "Tuning T-cell receptor affinity to optimize clinical risk-benefit when targeting α-fetoprotein (AFP) positive liver cancer," which details the development of the SPEAR T-cells targeting AFP
Preclinical:
· Good progress with off-the-shelf product and presented progress to date at ASGCT (Free ASGCT Whitepaper) 2018
· Developing multiple next generation approaches — first candidate ready for IND submission in 2H 2019
·Investigated new targets and additional HLAs to be brought to the clinic beyond 2019
Well-developed preclinical package including proprietary methods for predicting binding of a TCR to an off-target peptide utilizing alanine scanning processes. A licensing program is available to third parties wishing to use this patented method.
Manufacturing:
· Routinely producing cell product at target doses across a broad range of solid tumor indications
· Navy Yard facility now capable of manufacturing cell product for up to 10 patients per month (scalable to 100 patients per year) with capacity for an additional 10 patients per month at a third-party supplier HCATs
· Implemented rapid sterility testing to decrease vein-to-vein time
· Routinely producing more than 5 billion cells to meet target doses
· Agreement with third-party vector manufacturer for commercial supply — batches manufactured for ADP-A2M10, ADP-A2M4, ADP-A2AFP, and next generation SPEAR T-cells
· In-house suspension vector manufacturing capacity with an engineering run completed and first production expected in 2019
NY-ESO Program (now transitioned to GSK):
· Myxoid/round cell liposarcoma: Initial responses observed in a second solid tumor indication with data presented at ASCO (Free ASCO Whitepaper) 2018 and updated at SITC (Free SITC Whitepaper) 2018
· Agreement with GSK:
· Completed transition of the NY-ESO SPEAR T-cell development program in August 2018
· GSK assumed full responsibility for future research, development, and potential commercialization of NY-ESO now called GSK3377794 (GSK ‘794)
· Adaptimmune received ~ $27.5 million (~£21.2 million) in 2018 from GSK for completion of the transition
Other corporate news:
·Completed Registered Direct Offering, raising total net proceeds of ~$100 million in September 2018
· Appointed John Furey as an independent Non-Executive Director, effective July 5, 2018, succeeding Dr. Peter Thompson
Financial Results for the fourth quarter and year ended December 31, 2018
·Cash / liquidity position: As of December 31, 2018, Adaptimmune had cash and cash equivalents of $68.4 million and Total Liquidity(1) of $205.1 million.
·Revenue: Revenue represents the upfront and milestone payments, which are recognized as delivered services to GSK. Revenue for the fourth quarter and year ended December 31, 2018 were $1.5 million and $59.5 million compared to $4.3 million and $37.8 million for the same periods of 2017. Revenue in the year ended December 31, 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 fourth quarter and year ended December 31, 2018 were $22.8 million and $98.3 million, compared to $25.1 million and $87.4 million for the same periods of 2017. The increase was primarily due to increased costs associated with clinical trials; costs of developing manufacturing capability in the Company’s U.S. facility and increased personnel expenses.
· General and administrative ("G&A") expenses: G&A expenses for the fourth quarter and year ended December 31, 2018 were $10.8 million and $43.6 million, compared $8.8 million and $31.1 million for the same periods of 2017. The increase was primarily due to increased personnel costs consistent with our planned growth an increase in costs associated with supporting and maintaining our IT infrastructure.
·Net loss: Net loss attributable to holders of the Company’s ordinary shares for the fourth quarter and year ended December 31, 2018 were $36.2 million and $95.5 million ($(0.16) per ordinary share) compared to $27.3 million and $70.1 million ($(0.13) per ordinary share) in the same periods of 2017.
Financial Guidance
The Company believes that its existing cash and cash equivalents, short-term deposits and marketable securities, Total Liquidity, will fund the Company’s current operating plan through to late 2020.
Conference Call Information
The Company will host a live teleconference and webcast to provide additional details at 8:00 a.m. EST (1:00 p.m. GMT) today, February 27, 2019. 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, if preferred, please dial (833) 652-5917 (U.S. or Canada) 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 (9455267).