Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell
reprogramming company advancing a diverse pipeline of cell
therapies for patients with solid tumors today reported financial
results and business highlights for the fourth quarter and year
ended December 31, 2022.
“Lyell continued to gain momentum in 2022 with the initiation of
two Phase 1 clinical trials for our wholly-owned CAR T cell
and TIL product candidates, and we head into 2023 with a goal of
accelerating this momentum to generate clinical data from these
trials as rapidly as possible,” said Lynn Seely, M.D., Lyell’s
President and CEO. “We continued to invest in our innovative
reprogramming technologies and recently announced two product
candidates in preclinical development that incorporate new
stackable technologies designed to further enhance T-cell potency
and cytotoxicity to defeat solid tumors. Our strong financial
position with cash runway into 2026 positions us to demonstrate the
value of our two lead clinical programs that target solid tumors
with large unmet needs while continuing to invest in and develop
our innovative pipeline.”
Fourth Quarter Updates and Recent
Business Highlights
Lyell is advancing four wholly-owned product candidates: two
product candidates, LYL797 and LYL845, are in Phase 1 clinical
development and two additional product candidates, LYL119 and a TIL
product candidate incorporating novel genetic and epigenetic
reprogramming technologies, are in preclinical development.
LYL797 – A ROR1 CAR T-cell product candidate genetically
reprogrammed using c-Jun and epigenetically reprogrammed using
Lyell’s proprietary Epi-RTM
manufacturing protocol, designed for differentiated potency
and durability
- Enrollment in the Phase 1 clinical
trial of LYL797 is ongoing. Initial clinical data from the Phase 1
trial of LYL797 are expected in the first half of 2024.
- Presented nonclinical data at the
American Association of Cancer Research 2022 Annual Meeting
characterizing LYL797 and demonstrating that Lyell’s c-Jun
overexpression and Epi-R reprogramming technologies can overcome
barriers of T-cell exhaustion and lack of durable stemness in
engineered T cells using a set of in vitro and in vivo models,
including an aggressive syngeneic mouse tumor model and a xenograft
lung cancer model.
- Presented nonclinical data
demonstrating LYL797 showed improved expansion and anti-tumor
activity and prolonged survival compared to conventional ROR1 CAR T
cells in an established human ROR1-positive H1975 mouse xenograft
model at the American Society of Gene and Cell Therapy Annual
Meeting.
LYL119 – An innovative ROR1 CAR T-cell product designed
for enhanced cytotoxicity
- LYL119 incorporates four of Lyell’s
stackable reprogramming technologies, including two novel
technologies – a genetic knockout of NR4A3 (NR4A3-KO) and Stim-R™.
These technologies, which are complementary to c-Jun and Epi-R, are
designed to further improve the anti-tumor potency and durability
of T-cells.
- An IND for LYL119 is expected to be
submitted in the first half of 2024.
- Presented nonclinical data
demonstrating that the combination of two genetic reprogramming
technologies, NR4A3 gene knockout and c-Jun overexpression,
enhances the functional activity of ROR1 CAR T cells as shown by
higher levels of cytokine production, increased CAR T-cell
persistence and reduced surface expression of inhibitory receptors
after repetitive antigen stimulation, as well as significant
improvement in tumor control in vivo at The Society for
Immunotherapy of Cancer 2022 Annual Meeting (SITC 2022).
- Presented nonclinical data at SITC 2022
demonstrating that Lyell’s proprietary Stim-R epigenetic
reprogramming technology, which enables precise control and
optimized delivery of activation molecules during T-cell
production, generates potent CAR T-cell product candidates with
increased cell proliferation and persistence, as well as improved
tumor control in vivo.
LYL845 – A novel epigenetically reprogrammed TIL product
candidate designed for differentiated potency and
durability
- Announced clearance of the IND for
LYL845 in October 2022; enrollment in the Phase 1 clinical trial
for LYL845 is ongoing. Initial clinical data from the Phase 1 trial
of LYL845 are expected in 2024.
- Presented nonclinical data at SITC 2022
demonstrating the ability of Lyell’s Epi-R technology to
successfully expand TIL in both hot and cold tumors and to retain
qualities linked with anti-tumor functionality and improved
outcomes in previous TIL clinical trials. These qualities present
in Lyell’s Epi-R TIL include a greater proportion of CD8+ T cells,
enrichment for T cells with stem-like profiles, better metabolic
fitness and preserved polyclonality compared to control TIL
preparations.
- Presented bioinformatic analyses,
including comprehensive analyses of transcriptomic profiles,
polyclonality and prediction of tumor-reactive T cell clones in
Lyell’s LYL845 product candidate, at SITC 2022. These analyses
demonstrated that LYL845 expanded at clinical scale using Epi-R
technology remained highly polyclonal and preserved approximately
94% of the predicted tumor reactive clones. Further, the preserved
predicted tumor reactive clones in LYL845 have increased stemness
and reduced exhaustion‑associated genes compared to TIL products
derived from the standard process.
Corporate and Operational Updates
- In December, Lynn Seely, M.D., a member
of the company’s board since May 2021 and former President and CEO
of Myovant Sciences, was named President and CEO. Dr. Seely has
extensive biopharmaceutical leadership experience with a track
record of success building companies and developing new medicines
in oncology and women’s health.
- In September, Rahsaan W. Thompson was
named Chief Legal Officer. Mr. Thompson is a biopharmaceutical
industry veteran with more than 20 years of experience with
development stage and commercial companies.
- In January, Gary Lee, Ph.D. was named
Chief Scientific Officer. Dr. Lee is a veteran biotech leader with
more than a decade of experience heading translational cell and
gene therapy programs.
Fourth Quarter and Full Year
2022 Financial Results
Lyell reported a net loss of $8.4 million and $183.1 million for
the fourth quarter and year ended December 31, 2022,
respectively, compared to a net loss of $83.7 million and $250.2
million for the same periods in 2021. Non‑GAAP net loss, which
excludes non-cash stock-based compensation, non-cash expenses
related to the change in the estimated fair value of success
payment liabilities and certain non-cash investment gains and
charges, was $0.3 million and $104.2 million for the
fourth quarter and year ended December 31, 2022, respectively,
compared to $41.7 million and $147.9 million for the same periods
in 2021.
Revenue
- Revenue was $48.4 million and $84.7
million for the fourth quarter and year ended December 31,
2022, respectively, compared to $2.8 million and $10.7 million for
the same periods in 2021. The increase in revenue was driven
primarily by recognizing the remaining deferred revenue from the
GSK collaboration agreement.
GAAP and Non-GAAP Operating Expenses
- Research and development (R&D)
expenses were $38.0 million and $159.2 million for the fourth
quarter and year ended December 31, 2022, respectively,
compared to $19.3 million and $138.7 million for the same periods
in 2021. The increase in fourth quarter 2022 R&D expenses was
primarily driven by non-cash expenses related to the change in the
estimated fair value of success payment liabilities. The increase
in annual 2022 R&D expenses was due primarily to increases in
personnel and infrastructure costs to support the expansion of our
R&D and manufacturing capabilities. Non‑GAAP R&D expenses,
which exclude non-cash stock-based compensation and non-cash
expenses related to the change in the estimated fair value of
success payment liabilities for the fourth quarter and year ended
December 31, 2022, were $41.0 million and
$147.6 million, respectively, compared to $32.2 million
and $119.7 million for the same periods in 2021.
- General and administrative (G&A)
expenses were $26.3 million and $117.3 million for the fourth
quarter and year ended December 31, 2022, respectively,
compared to $31.9 million and $89.1 million for the same periods in
2021. The decrease in fourth quarter 2022 and increase in annual
2022 G&A expenses were both primarily driven by changes in
non-cash stock-based compensation. Non‑GAAP G&A expenses, which
exclude non-cash stock-based compensation, for the fourth quarter
and year ended December 31, 2022 were $12.3 million and
$52.1 million, respectively, compared to $13.4 million
and $42.2 million for the same periods in 2021. The increase
in annual 2022 non-GAAP G&A expenses was driven by increased
legal and corporate expenses and public company operating
costs.
A discussion of non-GAAP financial measures, including
reconciliations of the most comparable GAAP measures to non‑GAAP
financial measures, is presented below under “Non-GAAP Financial
Measures.”
Cash, cash equivalents and marketable securities
Cash, cash equivalents and marketable securities as of
December 31, 2022 were $710.3 million, compared to
$898.3 million as of December 31, 2021. Lyell believes
that its cash, cash equivalents and marketable securities balances
will be sufficient to meet working capital and capital expenditure
needs into 2026.
About Lyell Immunopharma, Inc.
Lyell is a clinical-stage T-cell reprogramming company advancing
a diverse pipeline of cell therapies for patients with solid
tumors. The technologies powering its product candidates are
designed to address barriers that limit consistent and long-lasting
responses to cell therapy for solid tumors: T-cell exhaustion and
lack of durable stemness, which includes the ability to persist and
self-renew to drive durable tumor cytotoxicity. Lyell is applying
its proprietary ex vivo genetic and epigenetic reprogramming
technologies to address these barriers in order to develop new
medicines with improved durable clinical outcomes. Lyell is based
in South San Francisco, California with facilities in Seattle and
Bothell, Washington. To learn more, please visit www.lyell.com.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. Forward-looking statements expressed or implied in this press
release include, but are not limited to, statements regarding:
Lyell’s anticipated progress, business plans, business strategy and
clinical trials; Lyell advancing its pipeline or growing its
capabilities; the potential clinical benefits and therapeutic
potential of Lyell’s product candidates; Lyell’s expectation that
its strong financial position with cash runway into 2026 will
enable it to demonstrate the value of its two lead clinical
programs and continue to invest in and develop its pipeline;
expected milestones; enrollment expectations for the Phase 1
clinical trials of LYL797 and LYL845; the timing of initial
clinical data from Lyell’s planned Phase 1 trials for LYL797 and
LYL845; and other statements that are not historical fact. These
statements are based on Lyell’s current plans, objectives,
estimates, expectations and intentions, are not guarantees of
future performance and inherently involve significant risks and
uncertainties. Actual results and the timing of events could differ
materially from those anticipated in such forward-looking
statements as a result of these risks and uncertainties, which
include, but are not limited to, risks and uncertainties related
to: the effects of geopolitical instability; macroeconomic
conditions and the ongoing COVID-19 pandemic; Lyell’s ability to
submit planned INDs or initiate or progress clinical trials on the
anticipated timelines, if at all; Lyell’s lack of experience as a
company in enrolling, conducting or completing clinical trials;
Lyell’s ability to manufacture and supply its product candidates
for its clinical trials; the nonclinical profiles of Lyell’s
product candidates not translating in clinical trials; the
potential for results from clinical trials to differ from
nonclinical, early clinical, preliminary or expected results;
significant adverse events, toxicities or other undesirable side
effects associated with Lyell’s product candidates; the significant
uncertainty associated with Lyell’s product candidates ever
receiving any regulatory approvals; Lyell’s ability to obtain,
maintain or protect intellectual property rights related to its
product candidates; implementation of Lyell’s strategic plans for
its business and product candidates; the sufficiency of Lyell’s
capital resources and need for additional capital to achieve its
goals; and other risks, including those described under the heading
“Risk Factors” in Lyell’s Quarterly Report on Form 10-Q for the
quarter ended September 30, 2022, filed with the Securities and
Exchange Commission (SEC) on November 8, 2022, and its Annual
Report on Form 10-K for the year ended December 31, 2022,
being filed with the SEC today. Forward-looking statements
contained in this press release are made as of this date, and Lyell
undertakes no duty to update such information except as required
under applicable law.
Lyell Immunopharma, Inc.
Unaudited Selected Consolidated Financial
Data
(in thousands)
Statement of Operations Data:
|
Three Months Ended December 31, 2022 |
|
Year Ended December 31, |
|
|
2022 |
|
|
|
2021 |
|
|
|
2022 |
|
|
|
2021 |
|
Revenue |
$ |
48,386 |
|
|
$ |
2,822 |
|
|
$ |
84,683 |
|
|
$ |
10,650 |
|
Operating expenses: |
|
|
|
|
|
|
|
Research and development |
|
38,032 |
|
|
|
19,285 |
|
|
|
159,188 |
|
|
|
138,693 |
|
General and administrative |
|
26,348 |
|
|
|
31,873 |
|
|
|
117,307 |
|
|
|
89,057 |
|
Other operating income, net |
|
(1,210 |
) |
|
|
(798 |
) |
|
|
(4,754 |
) |
|
|
(2,324 |
) |
Total operating expenses |
|
63,170 |
|
|
|
50,360 |
|
|
|
271,741 |
|
|
|
225,426 |
|
Loss from operations |
|
(14,784 |
) |
|
|
(47,538 |
) |
|
|
(187,058 |
) |
|
|
(214,776 |
) |
Interest income, net |
|
3,453 |
|
|
|
323 |
|
|
|
7,053 |
|
|
|
1,165 |
|
Other income (expense), net |
|
2,934 |
|
|
|
(44 |
) |
|
|
1,887 |
|
|
|
(161 |
) |
Impairment of other investments |
|
— |
|
|
|
(36,447 |
) |
|
|
(5,000 |
) |
|
|
(36,447 |
) |
Total other income (loss), net |
|
6,387 |
|
|
|
(36,168 |
) |
|
|
3,940 |
|
|
|
(35,443 |
) |
Net loss |
$ |
(8,397 |
) |
|
$ |
(83,706 |
) |
|
$ |
(183,118 |
) |
|
$ |
(250,219 |
) |
Balance Sheet Data:
|
As of December 31, |
|
|
2022 |
|
|
2021 |
|
|
|
|
Cash, cash equivalents and
marketable securities |
$ |
710,269 |
|
$ |
898,325 |
Property and equipment,
net |
$ |
123,023 |
|
$ |
120,098 |
Total assets |
$ |
937,561 |
|
$ |
1,127,406 |
Total stockholders’
equity |
$ |
833,252 |
|
$ |
929,787 |
Non-GAAP Financial Measures
To supplement our financial results and guidance presented in
accordance with U.S. generally accepted accounting principles
(GAAP), we present non-GAAP net loss, non-GAAP R&D expenses and
non-GAAP G&A expenses. Non‑GAAP net loss and non-GAAP R&D
expenses exclude non-cash stock-based compensation expense and
non-cash expenses related to the change in the estimated fair value
of success payment liabilities from GAAP net loss and GAAP R&D
expenses. Non-GAAP net loss further adjusts non-cash investment
gains and charges, as applicable, and for the income tax effect, if
any, of the non-GAAP adjustments. Non‑GAAP G&A expenses exclude
non-cash stock-based compensation expense from GAAP G&A
expenses. We believe that these non-GAAP financial measures, when
considered together with our financial information prepared in
accordance with GAAP, can enhance investors’ and analysts’ ability
to meaningfully compare our results from period to period, and to
identify operating trends in our business. We have excluded
stock-based compensation expense, non-cash expenses related to the
change in the estimated fair value of success payment liabilities
and non-cash investment gains and charges from our non-GAAP
financial measures because they are non-cash gains and charges that
may vary significantly from period to period as a result of changes
not directly or immediately related to the operational performance
for the periods presented. We also regularly use these non-GAAP
financial measures internally to understand, manage and evaluate
our business and to make operating decisions. These non-GAAP
financial measures are in addition to, and not a substitute for or
superior to, measures of financial performance prepared in
accordance with GAAP. In addition, these non-GAAP financial
measures have no standardized meaning prescribed by GAAP and are
not prepared under any comprehensive set of accounting rules or
principles and, therefore, have limits in their usefulness to
investors. We encourage investors to carefully consider our results
under GAAP, as well as our supplemental non-GAAP financial
information, to more fully understand our business.
Lyell Immunopharma, Inc.
Unaudited Reconciliation of GAAP to
Non-GAAP Net Loss
(in thousands)
|
Three Months Ended December 31, |
|
Year Ended December 31, |
|
|
2022 |
|
|
|
2021 |
|
|
|
2022 |
|
|
|
2021 |
|
Net loss - GAAP |
$ |
(8,397 |
) |
|
$ |
(83,706 |
) |
|
$ |
(183,118 |
) |
|
$ |
(250,219 |
) |
Adjustments: |
|
|
|
|
|
|
|
Stock-based compensation expense |
|
18,363 |
|
|
|
21,178 |
|
|
|
81,924 |
|
|
|
62,201 |
|
Change in the estimated fair value of success payment
liabilities |
|
(7,307 |
) |
|
|
(15,630 |
) |
|
|
(5,130 |
) |
|
|
3,713 |
|
Impairment of other investments |
|
— |
|
|
|
36,447 |
|
|
|
5,000 |
|
|
|
36,447 |
|
Gain on other investments |
|
(2,923 |
) |
|
|
— |
|
|
|
(2,923 |
) |
|
|
— |
|
Net loss - Non-GAAP(1) |
$ |
(264 |
) |
|
$ |
(41,711 |
) |
|
$ |
(104,247 |
) |
|
$ |
(147,858 |
) |
(1) There was
no income tax effect related to the adjustments made to calculate
non-GAAP net loss because of the full valuation allowance on our
net U.S. deferred tax assets for all periods presented.
Lyell Immunopharma, Inc.
Unaudited Reconciliation of GAAP to
Non-GAAP Research and Development Expenses
(in thousands)
|
Three Months Ended December 31, |
|
Year Ended December 31, |
|
|
2022 |
|
|
|
2021 |
|
|
|
2022 |
|
|
|
2021 |
|
Research and development -
GAAP |
$ |
38,032 |
|
|
$ |
19,285 |
|
|
$ |
159,188 |
|
|
$ |
138,693 |
|
Adjustments: |
|
|
|
|
|
|
|
Stock-based compensation expense |
|
(4,320 |
) |
|
|
(2,713 |
) |
|
|
(16,721 |
) |
|
|
(15,328 |
) |
Change in the estimated fair value of success payment
liabilities |
|
7,307 |
|
|
|
15,630 |
|
|
|
5,130 |
|
|
|
(3,713 |
) |
Research and development -
Non-GAAP |
$ |
41,019 |
|
|
$ |
32,202 |
|
|
$ |
147,597 |
|
|
$ |
119,652 |
|
Lyell Immunopharma, Inc.
Unaudited Reconciliation of GAAP to
Non-GAAP General and Administrative Expenses
(in thousands)
|
Three Months Ended December 31, |
|
Year Ended December 31, |
|
|
2022 |
|
|
|
2021 |
|
|
|
2022 |
|
|
|
2021 |
|
General and administrative -
GAAP |
$ |
26,348 |
|
|
$ |
31,873 |
|
|
$ |
117,307 |
|
|
$ |
89,057 |
|
Adjustments: |
|
|
|
|
|
|
|
Stock-based compensation expense |
|
(14,043 |
) |
|
|
(18,465 |
) |
|
|
(65,203 |
) |
|
|
(46,873 |
) |
General and administrative -
Non-GAAP |
$ |
12,305 |
|
|
$ |
13,408 |
|
|
$ |
52,104 |
|
|
$ |
42,184 |
|
Contact:
Ellen Rose
Senior Vice President, Communications and Investor Relations
erose@lyell.com
Lyell Immunopharma (NASDAQ:LYEL)
Gráfica de Acción Histórica
De Abr 2024 a May 2024
Lyell Immunopharma (NASDAQ:LYEL)
Gráfica de Acción Histórica
De May 2023 a May 2024