Xilio Therapeutics, Inc. (Nasdaq: XLO), a biotechnology
company developing tumor-activated immuno-oncology therapies for
people living with cancer, today announced pipeline progress,
business updates and reported financial results for the third
quarter ended September 30, 2022.
“We continued to make meaningful progress advancing our
clinical-stage cytokine programs, XTX202 and XTX301, during the
quarter,” said René Russo, Pharm.D., chief executive officer of
Xilio. “XTX202, our tumor-activated IL-2, has successfully reached
the target dose range of 1 mg/kg in an outpatient setting in our
ongoing Phase 1 clinical trial with no signs of vascular leak
syndrome, and preliminary clinical data indicate evidence of IL-2
specific biology, including intra-tumoral pharmacodynamic effects
in one patient for whom a tumor biopsy was available. We expect to
report initial anti-tumor activity data for XTX202 in the third
quarter of 2023. In addition, with the recent FDA clearance of our
IND application for XTX301, our tumor-activated IL-12, we look
forward to initiating a Phase 1 clinical trial in the first quarter
of 2023 and evaluating the therapeutic potential of XTX301 across
‘cold’ and ‘hot’ tumor types.”
Dr. Russo continued, “While we remain enthusiastic about the
potential for XTX101, our tumor-activated anti-CTLA-4, we plan to
focus our existing resources on advancing our clinical-stage
cytokine programs, and we will seek to partner XTX101 to advance
the program beyond the ongoing Phase 1 monotherapy cohorts.”
Pipeline and Business
Updates
XTX202: tumor-activated, engineered
IL-2
XTX202 is an investigational tumor-activated beta-gamma biased
(non-alpha), engineered IL‑2 molecule designed to potently
stimulate CD8+ effector T cells and natural killer (NK) cells
without concomitant stimulation of regulatory T cells when
activated (unmasked) in the tumor microenvironment. XTX202 is
currently being evaluated in monotherapy dose-escalation of an
ongoing Phase 1 clinical trial in patients with advanced solid
tumors.
- Xilio recently began dosing patients at the 1 mg/kg dose level,
which is in the target clinical dose range for XTX202, making it
one of the first engineered IL-2 molecules to achieve a dose that
is in line with that of traditional high dose treatment with
aldesleukin.
- As of November 7, 2022, 11 patients have been treated with
XTX202 as outpatients in monotherapy dose-escalation at four dose
levels ranging from 0.27 mg/kg to 1.0 mg/kg.
- Preliminary analyses indicated evidence of IL-2 specific
biology in patients consistent with data observed in preclinical
studies, including CD8+ effector T cells and NK cells increasing in
peripheral circulation steadily over time.
- No signs of vascular leak syndrome (VLS) or decreases in
albumin (an early sign of VLS) have been observed in patients to
date.
- In addition, Xilio today reported preliminary intra-tumoral
pharmacodynamic data for a single patient treated with XTX202 who
had an optional on-treatment tumor biopsy and was the first patient
for whom a tumor biopsy analysis was available to date. This
patient tumor biopsy featured increased numbers of stromal tumor
infiltrating lymphocytes (TILs), increased frequency of CD8+
effector T cells among these TILs and decreased frequency of immune
suppressive regulatory T cells (TREGs). Importantly, in this
patient, at the time of the tumor biopsy, these changes occurred in
the absence of peripheral changes to either CD8+ effector T cells
or TREGs.
- A maximum tolerated dose has not yet been determined, and
enrollment in monotherapy dose-escalation is ongoing.
Xilio anticipates multiple milestones for XTX202 through the end
of 2023:
- Initiate patient enrollment in a monotherapy expansion cohort
of the Phase 1 clinical trial in the fourth quarter of 2022.
- Initiate patient enrollment in a Phase 2 monotherapy clinical
trial in the first half of 2023.
- Report preliminary anti-tumor activity and safety data from the
Phase 1/2 clinical trial in the third quarter of 2023.
XTX301: tumor-activated, engineered
IL-12
XTX301 is an investigational tumor-activated, engineered IL‑12
molecule designed to potently stimulate anti-tumor immunity and
reprogram the tumor microenvironment (TME) of poorly immunogenic
“cold” tumors towards an inflamed, or “hot,” state. IL‑12 plays a
key role in bridging innate and adaptive cellular immunity, making
it a compelling target for immunotherapy. However, life-threatening
toxicity observed with systemically active IL‑12, including severe
liver toxicity, have limited the therapeutic potential of IL‑12
agents. Preclinical studies using a murine surrogate molecule for
XTX301 demonstrated in vivo anti-tumor activity at doses as low as
0.04 mg/kg, and XTX301 demonstrated favorable tolerability in
non-human primates at doses up to 2 mg/kg given weekly over four
cycles.
- Xilio today announced that the U.S. Food and Drug
Administration has cleared the company’s investigational new drug
(IND) application for the evaluation of XTX301 as a potential
treatment for patients with advanced solid tumors.
Xilio anticipates multiple milestones for XTX301 through the end
of 2023:
- Initiate patient enrollment in monotherapy dose-escalation in a
Phase 1 clinical trial in the first quarter of 2023 evaluating the
safety and tolerability of XTX301 in patients with advanced solid
tumors.
- Report preliminary safety data from the Phase 1 clinical trial
in the fourth quarter of 2023.
XTX101: tumor-activated
anti-CTLA-4
XTX101, an Fc-enhanced, tumor-activated anti-CTLA-4, is
currently being evaluated in monotherapy dose-escalation of an
ongoing Phase 1 clinical trial in patients with advanced solid
tumors.
- Xilio is currently dosing patients at 150 mg once every six
weeks (Q6W) in the monotherapy dose-escalation cohort, which the
company anticipates completing by the end of 2022. Enrollment in a
monotherapy dose expansion cohort is currently ongoing.
- Preliminary pharmacokinetic (PK) analyses continue to
demonstrate dose-proportional drug exposure, with limited active
(unmasked) XTX101 in peripheral circulation consistent with PK data
observed in preclinical studies.
- Xilio anticipates reporting preliminary data from the Phase 1
clinical trial in the second quarter of 2023.
- Xilio plans to continue to explore opportunities for strategic
collaborations to advance XTX101 and does not plan to initiate an
anti-PD-1 combination cohort in the Phase 1 clinical trial or
initiate a Phase 2 clinical trial for XTX101 without a
partner.
Corporate
Highlights
- In September 2022, Xilio announced the appointment of Tomas J.
Heyman as a member of the board of directors and John Maraganore,
Ph.D. joined as a strategic advisor to the company.
- In August 2022, Xilio announced the promotion of Uli Bialucha,
Ph.D. to Chief Scientific Officer and Chris Frankenfield to Chief
Legal and Administrative Officer.
Upcoming
Presentations
Xilio will present a poster outlining preclinical data
demonstrating anti-tumor activity and sustained memory T-cell
response in mice for XTX202 in combination with immune checkpoint
blockade at the Society for Immunotherapy in Cancer 37th Annual
Meeting.
- Presentation title: XTX202, a
tumor-activated protein-engineered IL-2, exhibited enhanced
anti-tumor activity in combination with checkpoint inhibition in
mice
- Session date and time:
Thursday, November 11, 2022, at 11:40 am to 1:10 pm and 7:30 pm to
9:00 pm ET
- Abstract number: 841
Uli Bialucha, Ph.D., Xilio’s chief scientific officer, will
present at the 14th Annual Protein & Antibody Engineering
Summit (PEGS) Europe meeting and will highlight preclinical data
for XTX301, a tumor-activated IL-12, and Xilio’s emerging research
portfolio developing tumor-activated multifunctional biologics.
- Presentation title:
Engineering Tumor-Selective Biologics for Immune-Oncology
- Session date and time:
Monday, November 14, 2022, at 3:20 pm CET (10:20 am ET)
Third Quarter 2022 Financial
Results
- Cash Position: Cash and
cash equivalents were $139.1 million as of September 30, 2022,
compared to $198.1 million as of December 31, 2021.
- Research & Development (R&D)
Expenses: R&D expenses were $13.0
million for the third quarter of 2022, compared to $10.5 million
for the third quarter of 2021. The increase was primarily driven by
higher personnel-related costs mainly due to increased headcount
and a $0.2 million increase in non-cash equity-based compensation
expense, as well as increased costs associated with XTX301
preclinical, clinical and manufacturing development
activities.
- General & Administrative (G&A)
Expenses: G&A expenses were $7.2 million
for the third quarter of 2022, compared to $5.5 million for the
third quarter of 2021. The increase was primarily driven by higher
personnel-related costs, primarily due to increased headcount and a
$0.6 million increase in non-cash equity-based compensation
expense, as well as certain costs related to operating as a
publicly traded company.
- Net Loss: Net loss was
$19.8 million for the third quarter of 2022, compared to $16.3
million for the third quarter of 2021.
Financial Guidance
Xilio anticipates that its existing cash and cash equivalents
will be sufficient to fund its operating expenses and capital
expenditure requirements into the second quarter of 2024.
About the Phase 1/2 Clinical Trial for
XTX202 (IL-2)
The Phase 1 clinical trial for XTX202 is a first-in-human,
multi-center, open-label trial designed to evaluate the safety and
tolerability of XTX202 as a monotherapy in patients with advanced
solid tumors. The Phase 1 clinical trial is designed to enroll up
to approximately 119 patients across all cohorts at multiple sites
in the United States, Europe and other international sites. Please
refer to NCT05052268 on www.clinicaltrials.gov for additional
details.
The Phase 2 clinical trial for XTX202 is a multi-center,
open-label trial designed to evaluate the safety and efficacy of
XTX202 as a monotherapy in patients with melanoma and renal cell
carcinoma at the recommended Phase 2 dose. The Phase 2 clinical
trial is designed to enroll up to approximately 70 patients in the
United States and Europe. Please refer to NCT05052268 on
www.clinicaltrials.gov for additional details.
About the Planned Phase 1 Clinical Trial
for XTX301 (IL-12)
The planned Phase 1 clinical trial for XTX301 is a
first-in-human, multi-center, open-label trial designed to evaluate
the safety and tolerability of XTX301 as a monotherapy in patients
with advanced solid tumors. The Phase 1 clinical trial is designed
to enroll up to approximately 94 patients across all cohorts at
multiple sites in the United States.
About the Phase 1 Clinical Trial for
XTX101 (anti-CTLA-4)
XTX101 is an investigational Fc-enhanced, tumor-activated
anti-CTLA-4 monoclonal antibody designed to deplete regulatory T
cells when activated (unmasked) in the TME. The Phase 1 clinical
trial is a first-in-human, multi-center, open-label trial designed
to evaluate the safety and tolerability of XTX101 for the treatment
of adult patients with advanced solid tumors. Please refer to
NCT04896697 on www.clinicaltrials.gov for additional
details.
About Xilio
Therapeutics
Xilio Therapeutics is a clinical-stage biotechnology company
discovering and developing tumor-activated immuno-oncology (I-O)
therapies with the goal of significantly improving outcomes for
people living with cancer without the systemic side effects of
current I-O treatments. The company is using its proprietary
platform to build a pipeline of novel, tumor-activated molecules,
including cytokines and other biologics, which are designed to
optimize their therapeutic index and localize anti-tumor activity
within the tumor microenvironment. Xilio is currently advancing
multiple programs for tumor-activated I-O treatments in clinical
development, as well as programs in preclinical development. Learn
more by visiting www.xiliotx.com and follow us on Twitter
(@xiliotx) and LinkedIn (Xilio Therapeutics, Inc.).
Cautionary Note Regarding
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, statements
regarding plans, timing and expectations related to the initiation
of patient enrollment in a monotherapy expansion cohort for the
Phase 1 clinical trial for XTX202, the initiation of patient
enrollment in a Phase 2 clinical trial for XTX202 and reporting
data from the Phase 1/2 clinical trial for XTX202; plans, timing
and expectations related to the initiation of patient enrollment in
the planned Phase 1 clinical trial for XTX301 and reporting data
from the Phase 1 clinical trial for XTX301; plans, timing and
expectations related to completing monotherapy dose-escalation for
the Phase 1 clinical trial for XTX101 and reporting data from the
Phase 1 clinical trial for XTX101; plans, timing and expectations
related to potential collaborations to advance XTX101; plans,
timing and expectations related to progressing its next
research-stage program; the potential benefits of any of Xilio’s
current or future product candidates in treating patients; Xilio’s
ability to fund its operating expenses and capital expenditure
requirements with its existing cash and cash equivalents; and
Xilio’s strategy, goals and anticipated financial performance,
milestones, business plans and focus. The words “aim,” “may,”
“will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,”
“intend,” “believe,” “estimate,” “predict,” “project,” “potential,”
“continue,” “seek,” “target” and similar expressions are intended
to identify forward-looking statements, although not all
forward-looking statements contain these identifying words. Any
forward-looking statements in this press release are based on
management’s current expectations and beliefs and are subject to a
number of important risks, uncertainties and other factors that may
cause actual events or results to differ materially from those
expressed or implied by any forward-looking statements contained in
this press release, including, without limitation, risks and
uncertainties related to ongoing and planned research and
development activities, including initiating, conducting or
completing preclinical studies and clinical trials and the timing
and results of such preclinical studies or clinical trials; the
delay of any current or planned preclinical studies or clinical
trials or the development of Xilio’s current or future product
candidates; Xilio’s ability to obtain and maintain sufficient
preclinical and clinical supply of current or future product
candidates; Xilio’s advancement of multiple early-stage programs;
there can be no assurance that interim or preliminary preclinical
or clinical data or results will be predictive of future
preclinical or clinical data or results, including, without
limitation, the preliminary intra-tumoral pharmacodynamic data
reported for a single patient treated with XTX202 who had an
optional on-treatment tumor biopsy and was the first patient for
whom a tumor biopsy analysis was available as of the date hereof;
Xilio’s ability to successfully demonstrate the safety and efficacy
of its product candidates and gain approval of its product
candidates on a timely basis, if at all; results from preclinical
studies or clinical trials for Xilio’s product candidates, which
may not support further development of such product candidates;
actions of regulatory agencies, which may affect the initiation,
timing and progress of current or future clinical trials; Xilio’s
ability to obtain, maintain and enforce patent and other
intellectual property protection for current or future product
candidates; Xilio’s ability to obtain and maintain sufficient cash
resources to fund current or future operating expenses and capital
expenditure requirements; the impact of international trade
policies on Xilio’s business, including U.S. and China trade
policies; and Xilio’s ability to seek, establish and maintain a
collaboration or partnership to develop XTX101 with a collaborator
or partner. These and other risks and uncertainties are described
in greater detail in the sections entitled “Risk Factor Summary”
and “Risk Factors” in Xilio’s filings with the U.S. Securities and
Exchange Commission (SEC), including Xilio’s most recent Quarterly
Report on Form 10‑Q and any other filings that Xilio has made
or may make with the SEC in the future. Any forward-looking
statements contained in this press release represent Xilio’s views
only as of the date hereof and should not be relied upon as
representing its views as of any subsequent date. Except as
required by law, Xilio explicitly disclaims any obligation to
update any forward-looking statements.
This press release contains hyperlinks to information that is
not deemed to be incorporated by reference in this press
release.
For Investor Inquiries:Myles
CloustonVice President, Investor Relationsinvestors@xiliotx.com
For Media Inquiries: Julissa
Viana Vice President, Corporate Communications
media@xiliotx.com
XILIO
THERAPEUTICS, INC.
Condensed Consolidated Balance
Sheets(In
thousands)(Unaudited)
|
|
|
|
|
|
|
|
|
|
|
September
30, |
|
December 31, |
|
|
2022 |
|
2021 |
Assets |
|
|
|
|
|
|
|
|
Cash and cash equivalents |
|
$ |
139,143 |
|
|
$ |
198,053 |
|
Other assets |
|
|
18,271 |
|
|
|
20,007 |
|
Total assets |
|
$ |
157,414 |
|
|
$ |
218,060 |
|
Liabilities
and Stockholders’ Equity |
|
|
|
|
|
|
|
|
Liabilities |
|
$ |
31,116 |
|
|
$ |
32,631 |
|
Stockholders’ equity |
|
|
126,298 |
|
|
|
185,429 |
|
Total liabilities and stockholders’ equity |
|
$ |
157,414 |
|
|
$ |
218,060 |
|
XILIO
THERAPEUTICS, INC.
Condensed Consolidated Statements
of Operations and Comprehensive
Loss(In thousands, except share
and per share
data)(Unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended
September 30, |
|
Nine Months Ended
September 30, |
|
|
2022 |
|
2021 |
|
2022 |
|
2021 |
Operating expenses(1) |
|
|
|
|
|
|
|
|
|
|
|
|
Research and development |
|
$ |
13,038 |
|
|
$ |
10,470 |
|
|
$ |
44,204 |
|
|
$ |
39,836 |
|
General and administrative |
|
|
7,168 |
|
|
|
5,491 |
|
|
|
21,778 |
|
|
|
15,652 |
|
Total operating expenses |
|
|
20,206 |
|
|
|
15,961 |
|
|
|
65,982 |
|
|
|
55,488 |
|
Loss from operations |
|
|
(20,206 |
) |
|
|
(15,961 |
) |
|
|
(65,982 |
) |
|
|
(55,488 |
) |
Other income (expense),
net |
|
|
|
|
|
|
|
|
|
|
|
|
Other income (expense), net |
|
|
416 |
|
|
|
(290 |
) |
|
|
226 |
|
|
|
(611 |
) |
Total other income (expense), net |
|
|
416 |
|
|
|
(290 |
) |
|
|
226 |
|
|
|
(611 |
) |
Net loss and comprehensive
loss |
|
$ |
(19,790 |
) |
|
$ |
(16,251 |
) |
|
$ |
(65,756 |
) |
|
$ |
(56,099 |
) |
Net loss per share, basic and
diluted |
|
$ |
(0.72 |
) |
|
$ |
(21.27 |
) |
|
$ |
(2.40 |
) |
|
$ |
(76.18 |
) |
Weighted average common shares
outstanding, basic and diluted |
|
|
27,399,906 |
|
|
|
763,869 |
|
|
|
27,384,085 |
|
|
|
736,416 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(1) Operating expenses include the following amounts of non-cash
equity-based compensation expense:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended
September 30, |
|
Nine Months Ended
September 30, |
|
|
2022 |
|
2021 |
|
2022 |
|
|
2021 |
|
Research and development
expense |
|
$ |
594 |
|
|
$ |
378 |
|
|
$ |
1,827 |
|
|
$ |
864 |
|
General and administrative
expense |
|
|
1,277 |
|
|
|
713 |
|
|
|
4,782 |
|
|
|
2,023 |
|
Total equity-based compensation expense |
|
$ |
1,871 |
|
|
$ |
1,091 |
|
|
$ |
6,609 |
|
|
$ |
2,887 |
|
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