Xilio Therapeutics, Inc. (Nasdaq: XLO), a biotechnology company
developing tumor-selective immuno-oncology therapies for people
living with cancer, today announced pipeline and business updates
and reported financial results for the second quarter ended June
30, 2022.
“We are encouraged by the preliminary
dose-escalation data reported today for XTX101, a tumor-selective
anti-CTLA-4. These data provide initial clinical validation of
Xilio’s geographically precise solutions (GPS) platform and
demonstrate that XTX101 has reached dose levels above the target
dose with limited active (unmasked) molecule in peripheral
circulation. Based on these data, we plan to explore a Phase 2
clinical trial for XTX101 in microsatellite stable (MSS) colorectal
cancer,” said René Russo, Pharm.D., chief executive officer of
Xilio. “With a strong balance sheet and experienced leadership
team, we are well-positioned to continue to advance our pipeline
and anticipate multiple clinical data milestones for XTX101 and
XTX202 in 2023.”
XTX101: Preliminary Dose-Escalation Data
from Ongoing Phase 1 Clinical Trial
XTX101, an Fc-enhanced, tumor-selective
anti-CTLA-4, is being evaluated in a Phase 1 clinical trial in
patients with advanced solid tumors. The target dose level for
XTX101 of 60 mg is anticipated to provide anti-tumor activity
similar to ipilimumab at 10 mg/kg (approximately 600 mg in a 60 kg
patient) based on the 10 times greater potency observed for XTX101
relative to an ipilimumab analogue in preclinical studies.
As of August 5, 2022, 12 patients have been
treated with XTX101 in the monotherapy dose-escalation cohort (Part
1A) at four dose levels ranging from 7 mg to 180 mg:
- The 180 mg dose level has surpassed the 60 mg target dose level
for XTX101. As a result, Xilio recently expanded enrollment at the
180 mg dose level.
- A maximum tolerated dose (MTD) has not yet been determined, and
enrollment in the dose-escalation cohort is ongoing.
- Preliminary pharmacokinetic (PK) analyses demonstrated
dose-proportional drug exposure, with limited active (unmasked)
XTX101 in peripheral circulation (range of % active in periphery:
6% - 16%) consistent with PK data observed in preclinical
studies.
Additional XTX101 Development Updates
- Xilio recently opened Part 1B of the clinical trial for patient
enrollment, which is a monotherapy cohort designed to evaluate
anti-tumor activity, including intra-tumoral PK and pharmacodynamic
(PD) data, in patients with anti-CTLA-4 sensitive tumor types, with
the goal of characterizing the anti-tumor activity of XTX101 at one
or more dose levels selected in Part 1A of the trial.
- Given the potential for Fc-enhanced anti-CTLA-4 agents like
XTX101 to demonstrate activity in tumors that are historically
resistant to immuno-oncology treatment, Xilio plans to explore
evaluating XTX101 in a Phase 2 clinical trial in patients with
microsatellite stable (MSS) colorectal cancer in combination with
an anti-PD(L)-1.
XTX202: Phase 1 Clinical Trial
Progress
XTX202, a tumor-selective, engineered IL-2, is
being evaluated in a Phase 1 clinical trial in patients with
advanced solid tumors. As of August 5, 2022, six patients have been
treated with XTX202 as outpatients in the monotherapy
dose-escalation cohort (Part 1A) at three dose levels ranging from
0.27 mg/kg to 0.53 mg/kg. An MTD has not yet been determined, and
enrollment in the dose-escalation cohort is ongoing.
Upcoming Anticipated
Milestones
Xilio anticipates multiple milestones through the
end of 2023:
XTX101
- Report data from Part 1A of the trial (monotherapy
dose-escalation cohort) supporting the recommended Phase 2 dose
(RP2D) in the first half of 2023. Xilio anticipates the data for
Part 1A will include available safety and anti-tumor activity, as
well as peripheral PK and PD data.
- Report preliminary data from Part 1B of the trial (monotherapy
expansion cohort) in the middle of 2023. Xilio anticipates the data
for Part 1B will include available safety and anti-tumor activity,
as well as intra-tumoral PK and PD data.
- Initiate patient enrollment in Part 1C of the trial
(pembrolizumab combination cohort) in the fourth quarter of
2022.
- Report preliminary data from Part 1C of the trial in the first
half of 2023. Xilio anticipates the data will include available
safety and anti-tumor activity, as well as peripheral PK and PD
data for XTX101 in combination with pembrolizumab.
XTX202
- Report data from Part 1A of the trial (monotherapy
dose-escalation cohort) supporting the RP2D in the first half of
2023. Xilio anticipates the data will include available safety and
anti-tumor activity, as well as peripheral PK and PD data.
- Initiate patient enrollment in Part 1B (monotherapy expansion
cohort) in the fourth quarter of 2022. Part 1B is a monotherapy
cohort designed to evaluate anti-tumor activity of XTX202 in a
basket of indications potentially sensitive to IL-2.
- Report preliminary data from Part 1B of the trial (monotherapy
expansion cohort) in the second half of 2023. Xilio anticipates the
data will include available safety and anti-tumor activity
data.
- Following the determination of a RP2D, Xilio anticipates
initiating a Phase 2 monotherapy trial in the first half of 2023
designed to evaluate the safety and efficacy of XTX202 in patients
with melanoma and renal cell carcinoma (RCC). Xilio anticipates
enrolling a total of approximately 35 patients across both cohorts
in the Phase 2 clinical trial.
XTX301
- Submit an investigational new drug application (IND) to the
U.S. Food and Drug Administration (FDA) for XTX301 in the fourth
quarter of 2022.
- Subject to FDA clearance of the IND, Xilio plans to initiate a
Phase 1 clinical trial in the first half of 2023 evaluating the
safety and tolerability of XTX301 as a monotherapy in patients with
advanced solid tumors. The Phase 1 clinical trial will consist of a
monotherapy dose-escalation cohort with the goal of determining a
RP2D for XTX301 and monotherapy expansion cohorts at the RP2D.
Corporate Highlights
- Today, Xilio announced the promotions of Uli Bialucha, Ph.D.,
to chief scientific officer and Chris Frankenfield to chief legal
and administrative officer, each effective as of August 8, 2022.
Dr. Bialucha previously served as the company’s senior vice
president of research since April 2021, and Mr. Frankenfield
previously served as the company’s general counsel since March
2021.
- In June 2022, Xilio announced the promotion of Martin Huber,
M.D., to president, the election of Paul Clancy as chair of the
board of directors, and the appointment of Robert Ross, M.D., as a
member of the board of directors.
- In May 2022, Xilio announced the appointment of Stacey Davis as
chief business officer.
Second Quarter 2022 Financial
Results
- Cash Position: Cash and cash equivalents
were $159.4 million as of June 30, 2022, compared to $198.1 million
as of December 31,
2021.
- Research & Development (R&D)
Expenses: R&D expenses were $16.2 million for the
second quarter of 2022, compared to $17.7 million for the second
quarter of 2021. The decrease was primarily driven by decreased
costs associated with XTX202 manufacturing and preclinical
activities, partially offset by increased costs associated with
XTX301, as well as higher personnel-related costs mainly due to
increased headcount, including a $0.3 million increase in non-cash
equity-based compensation expense.
- General & Administrative (G&A)
Expenses: G&A expenses were $8.3 million for the
second quarter of 2022, compared to $5.3 million for the second
quarter of 2021. The increase was primarily driven by higher
personnel-related costs, primarily due to increased headcount and a
$1.4 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 $24.6 million for
the second quarter of 2022, compared to $23.2 million for the
second quarter of 2021.
Financial Guidance
Xilio continues to anticipate that its existing
cash and cash equivalents will be sufficient to fund its operating
expenses and capital expenditure requirements into the first half
of 2024.
About the Phase 1 Clinical Trial for
XTX101
XTX101 is an investigational Fc-enhanced,
tumor-selective anti-CTLA-4 monoclonal antibody designed to deplete
regulatory T cells when activated selectively (unmasked) in the
tumor microenvironment (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 as a monotherapy, as well as
a combination therapy with pembrolizumab, for the treatment of
adult patients with advanced solid tumors. The Phase 1 portion of
the trial consists of three cohorts. The first cohort (Part 1A) is
an accelerated and standard 3+3 dose-escalation monotherapy cohort
designed to assess the tolerability of XTX101 in patients with
advanced solid tumors who have progressed after receiving the
standard-of-care treatment for their tumor. The second cohort (Part
1B) is a monotherapy cohort designed to evaluate evidence of
anti-CTLA-4 pharmacodynamic activity in patients who have
progressed on anti-PD-1 or anti-PD-L1 treatment but have not
received prior treatment with an anti-CTLA-4 therapy. The third
cohort (Part 1C) is a combination therapy cohort designed to
evaluate XTX101 in combination with pembrolizumab in patients who
have not previously been treated with an anti-PD-1 or anti-PD-L1
treatment. The Phase 1 clinical trial is designed to enroll a total
of up to approximately 104 patients across all cohorts at multiple
sites in the United States. Please refer to NCT04896697 on
www.clinicaltrials.gov for additional details.
In May 2021, Xilio entered into a clinical trial
collaboration and supply agreement with Merck & Co., Inc.
(known as MSD outside the US and Canada) to explore the therapeutic
potential of XTX101 in combination with pembrolizumab in patients
with advanced solid tumors.
About the Phase 1 Clinical Trial for
XTX202
XTX202 is an investigational tumor-selective
beta-gamma biased (non-alpha), engineered IL-2 molecule designed to
potently stimulate CD8 and natural killer (NK) cells without
concomitant stimulation of regulatory T cells when activated
selectively (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 XTX202 as a monotherapy in patients
with advanced solid tumors. The Phase 1 clinical trial is designed
to enroll a total of up to approximately 48 patients across all
cohorts at multiple sites in the United States. Please refer to
NCT05052268 on www.clinicaltrials.gov for additional details.
About XTX301
XTX301 is an investigational tumor-selective,
engineered IL-12 designed to potently stimulate anti-tumor immunity
and reprogram the 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, dose-limiting toxicities
observed with systemically active IL-12, including life-threatening
liver toxicity, have limited the therapeutic potential of IL-12
agents to date. 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 favorable tolerability. Xilio has
completed GLP toxicology studies for XTX301.
About Xilio Therapeutics
Xilio Therapeutics is a clinical-stage
biotechnology company focused on harnessing the immune system to
achieve deep and durable clinical responses to improve the lives of
patients with cancer. The company is using its proprietary
geographically precise solutions (GPS) platform to rapidly engineer
novel molecules, including cytokines and other biologics, that are
designed to optimize their therapeutic index. These molecules are
designed to localize activity within the tumor microenvironment
without systemic effects, resulting in the potential to achieve
enhanced anti-tumor activity. Xilio is building a pipeline of
wholly owned, tumor-selective, GPS-enabled cytokine and checkpoint
inhibitor product candidates, including its clinical-stage
programs, XTX101, a tumor-selective anti-CTLA-4 monoclonal
antibody, and XTX202, a tumor-selective IL-2, as well as its
earlier pipeline, including XTX301, a tumor-selective IL-12. For
more information, please visit 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
plans, timing and expectations for reporting data from Part 1A,
Part 1B and Part 1C of the Phase 1 clinical trial for XTX101; plans
to explore a Phase 2 clinical trial for XTX101 in MSS colorectal
cancer in combination with an anti-PD(L)-1; plans, timing and
expectations for reporting data from Part 1A and Part 1B of the
Phase 1 clinical trial for XTX202; plans to initiate a Phase 2
clinical trial for XTX202 in patients with melanoma and RCC,
including plans, timing and expectations for reporting preliminary
objective response rates for both indications; plans to submit an
IND to the FDA for XTX301; plans to initiate a Phase 1 clinical
trial for XTX301; 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; 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 the impact
of the COVID-19 pandemic on Xilio’s business, operations, strategy,
goals and anticipated milestones. 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: Melissa
Forst Argot Partners Xilio@argotpartners.com
For Media Inquiries: Julissa
Viana Vice President, Corporate Communications media@xiliotx.com
XILIO THERAPEUTICS, INC.
Condensed Consolidated Balance
Sheets (In thousands)
(Unaudited)
|
|
June 30, |
|
December 31, |
|
|
2022 |
|
2021 |
Assets |
|
|
|
|
|
|
|
|
Cash and cash equivalents |
|
$ |
159,410 |
|
|
$ |
198,053 |
|
Other assets |
|
|
18,717 |
|
|
|
20,007 |
|
Total assets |
|
$ |
178,127 |
|
|
$ |
218,060 |
|
Liabilities and Stockholders’ Equity |
|
|
|
|
|
|
|
|
Liabilities |
|
$ |
33,910 |
|
|
$ |
32,631 |
|
Stockholders’ equity |
|
|
144,217 |
|
|
|
185,429 |
|
Total liabilities and stockholders’ equity |
|
$ |
178,127 |
|
|
$ |
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 June
30, |
|
Six Months Ended June
30, |
|
|
2022 |
|
2021 |
|
2022 |
|
2021 |
Operating expenses (1) |
|
|
|
|
|
|
|
|
|
|
|
|
Research and development |
|
$ |
16,246 |
|
|
$ |
17,745 |
|
|
$ |
31,166 |
|
|
$ |
29,366 |
|
General and administrative |
|
|
8,306 |
|
|
|
5,262 |
|
|
|
14,610 |
|
|
|
10,161 |
|
Total operating expenses |
|
|
24,552 |
|
|
|
23,007 |
|
|
|
45,776 |
|
|
|
39,527 |
|
Loss from operations |
|
|
(24,552 |
) |
|
|
(23,007 |
) |
|
|
(45,776 |
) |
|
|
(39,527 |
) |
Other expense, net |
|
|
|
|
|
|
|
|
|
|
|
|
Other expense, net |
|
|
(61 |
) |
|
|
(174 |
) |
|
|
(190 |
) |
|
|
(321 |
) |
Total other expense, net |
|
|
(61 |
) |
|
|
(174 |
) |
|
|
(190 |
) |
|
|
(321 |
) |
Net loss and comprehensive loss |
|
$ |
(24,613 |
) |
|
$ |
(23,181 |
) |
|
$ |
(45,966 |
) |
|
$ |
(39,848 |
) |
Net loss per share, basic and diluted |
|
$ |
(0.90 |
) |
|
$ |
(31.48 |
) |
|
$ |
(1.68 |
) |
|
$ |
(55.16 |
) |
Weighted average common shares outstanding, basic and diluted |
|
|
27,384,614 |
|
|
|
736,473 |
|
|
|
27,376,043 |
|
|
|
722,424 |
|
____________(1) Operating
expenses include the following amounts of non-cash equity-based
compensation expense:
|
|
Three Months Ended June 30, |
|
Six Months Ended June 30, |
|
|
2022 |
|
2021 |
|
2022 |
|
|
2021 |
|
Research and development expense |
|
$ |
637 |
|
|
$ |
351 |
|
|
$ |
1,233 |
|
|
$ |
486 |
|
General and administrative expense |
|
|
2,072 |
|
|
|
651 |
|
|
|
3,505 |
|
|
|
1,310 |
|
Total equity-based compensation expense |
|
$ |
2,709 |
|
|
$ |
1,002 |
|
|
$ |
4,738 |
|
|
$ |
1,796 |
|
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