Prelude Therapeutics Incorporated (Prelude) (Nasdaq: PRLD), a
clinical-stage precision oncology company, today provides strategic
pipeline updates and reports third quarter financial results.
Recent clinical progress and strategic prioritization of the
pipeline include:
- First-in-class SMARCA2 degrader (PRT3789): Encouraging initial
clinical data including selective and dose-dependent SMARCA2
degradation, safety profile and robust enrollment of
biomarker-selected patients provide increased confidence in the
potential of PRT3789 to address a significant clinical need.
- Potentially best-in-class CDK9 inhibitor (PRT2527): Continued
demonstration of a differentiated safety profile, desired target
inhibition and the opportunity in multiple hematological cancers
support advancement of PRT2527 in patients with select B-cell
malignancies and AML.
- MCL-1 inhibitor (PRT1419): Phase 1 dose escalation in
hematological malignancies was completed. Given the overlap with
the CDK9 program, Prelude does not plan to advance PRT1419 further
at this time.
- CDK4/6 inhibitor (PRT3645): Phase 1 dose escalation data
demonstrated plasma drug exposure and target inhibition, reaching
levels needed for efficacy in preclinical models, at generally well
tolerated doses. Given the focus of the Company on SMARCA2 and
CDK9, Prelude will not advance the program further and is actively
pursuing further clinical development with external
partners.
“We made significant progress in the third quarter with our four
clinical stage molecules and, as planned, conducted a rigorous
assessment of each program. Based on this assessment, we are
prioritizing our resources on our first-in-class SMARCA2 degrader
molecules, IV and oral, and our potential best-in-class CDK9
inhibitor program,” stated Kris Vaddi, Ph.D., Chief Executive
Officer of Prelude. “We are confident that these two programs
represent compelling opportunities for demonstrating clinical
proof-of-concept in 2024, for advancing into potential Phase 2/3
registration studies, and for becoming important new medicines.
This decision reflects our dual commitment to deliver
differentiated treatments to patients and to build significant and
sustainable value for our shareholders.”
Dr. Vaddi continued, “Regarding our recently announced
partnership with AbCellera, this alliance combines our strengths in
small molecule drug discovery and development with AbCellera’s
powerful antibody discovery engine. We plan to build a portfolio of
first-in-class precision ADCs that will utilize highly selective
and potent small molecules and degraders as payloads targeting
critical oncogenic pathways. We have already started work on our
first program with a SMARCA payload on an antibody selected from a
lead panel of antibodies previously discovered by AbCellera. We
believe that this program further expands the potential of our
SMARCA2 selective degraders.”
Jane Huang, MD, President and Chief Medical Officer, said, “Our
SMARCA2 program continues to receive strong interest and support
from investigators as patients with deleterious SMARCA4 mutations
do not have effective treatment options. Based on our ability to
select patients using a readily available biomarker, we have been
able to enroll efficiently our ongoing Phase 1 clinical trial for
PRT3789. We are encouraged not only by the pace of enrollment but
also by early clinical data demonstrating selective degradation of
SMARCA2, and by the compound’s safety profile to date. Our top
priority is to generate initial clinical proof-of-concept data in
2024. Provided these results are as we expect, we anticipate
advancing the compound into a registrational Phase 2/3 trial
thereafter.”
“For our CDK9 inhibitor PRT2527, we are also encouraged by the
emerging data in both solid and hematological cancers. These data
demonstrate that our highly targeted compound has been generally
safe and well-tolerated with a strong inhibition of the pathway
required for efficacy in preclinical models and is
well-differentiated from other CDK9 inhibitors. These results
strengthen our confidence in its potential best-in-class profile
and position us to be the most advanced CDK9 inhibitor for patients
with B-cell malignancies and AML. Our key objective is to establish
clinical proof-of concept data in both the monotherapy setting and
in combinations in 2024.”
SMARCA Programs
PRT3789- SMARCA2 Targeted IV Protein Degrader
PRT3789 is a first-in-class highly selective degrader of SMARCA2
protein, which along with SMARCA4, controls gene regulation through
chromatin remodeling. Cancer cells with SMARCA4 mutations are
dependent on SMARCA2 for their growth and survival and selectively
degrading SMARCA2 induces cell death in cancer cells while sparing
normal cells. PRT3789 is efficacious and well-tolerated in
preclinical models of SMARCA4 deleted/mutated cancers as
monotherapy and in combination with standard of care. Prelude
believes a selective SMARCA2 degrader has the potential to be of
benefit in up to 70,000 US/EU cancer patients with the SMARCA4
mutation.
A Phase 1 multi-dose escalation clinical trial of PRT3789 is
ongoing (NCT05639751) in biomarker-selected SMARCA4 mutated
cancers. Prelude intends to evaluate PRT3789 as monotherapy as well
as in combination and plans to share initial Phase 1 data in
mid-2024.
SMARCA2 - Oral Program
Prelude recently nominated a potent, orally bioavailable and
highly selective SMARCA2 degrader candidate. This compound is
>1000x selective for SMARCA2 over SMARCA4 and is currently in
IND-enabling studies. Prelude expects to file an IND in the first
half of 2024.
SMARCA - Precision ADC
Prelude and its partner AbCellera began work on an early-stage
discovery program involving potent degraders of the SMARCA family
of proteins as payloads for novel antibodies targeting tumor
specific antigens. Given the potent anti-tumor activity of these
molecules in pre-clinical models of cancers beyond those targeted
by our SMARCA2 selective degraders, we believe that these precision
ADCs have the potential to extend the therapeutic utility of this
class.
CDK9 Inhibitor Program
Prelude believes its highly selective CDK9 inhibitor, PRT2527,
has the potential to avoid off-target toxicities, achieve
substantial clinical activity and become the best-in-class CDK9
inhibitor.
PRT2527 has completed a Phase 1 dose escalation study
(NCT05159518) in patients with solid tumors. In this trial, PRT2527
was shown to achieve high levels of target inhibition and to
potentially be better tolerated than existing CDK9 inhibitors,
specifically manageable neutropenia and an absence of meaningful
gastrointestinal events or hepatotoxicity.
The observed dose-dependent downregulation of MYC and MCL1 mRNA
expression, CDK9 transcriptional targets, was consistent with the
degree of target engagement required for preclinical efficacy. As
predicted by the preclinical models, 12 mg/m2 QW dosing showed
optimal target inhibition and has been selected as the optimal
dose. The overall safety profile observed in this study supports
further development of PRT2527 in hematologic malignancies
(NCT05665530) and this study is currently ongoing with initial
clinical data expected in mid 2024.
MCL1 Inhibitor Program
Prelude has concluded Phase 1 development of PRT1419 and
established a confirmation dose in hematological cancers. Based on
the potential to address the intended patient populations with the
CDK9 inhibitor which potently inhibits MCL-1, Prelude has made a
decision to prioritize its CDK9 inhibitor, PRT2527, over
PRT1419.
Next Generation CDK4/6 Inhibitor Program
PRT3645 is a highly potent and selective next generation CDK4/6
inhibitor with the potential to provide improved safety and
tolerability outcomes and to achieve higher, more effective brain
and tissue penetration than current CDK4/6 inhibitors.
Prelude intends to complete the dose escalation portion of the
Phase 1 clinical trial of PRT3645 this year. Prelude is actively
exploring continued clinical development with external
partners.
At the recent AACR-NCI-EORTC
International Conference on Molecular Targets and Cancer
Therapeutics, Prelude presented data showing that treatment with
PRT3645 was associated with substantial decreases in both pRb and
Ki67 expression, indicating a dose-dependent target engagement at
the doses evaluated. Also, PRT3645 treatment was generally well
tolerated in the initial three dose cohorts of patients with no
clinically meaningful gastrointestinal, hematologic or neurological
events reported to date, reflecting its enhanced selectivity
profile.
Third Quarter Financial
Results
Cash, Cash Equivalents and Marketable
Securities: Cash, cash equivalents, and marketable
securities as of September 30, 2023, were $230.5 million.
Prelude anticipates that its existing cash, cash equivalents and
marketable securities will fund Prelude’s operations into 2026.
Research and Development (R&D) Expenses:
For the third quarter of 2023, R&D expenses increased to
$26.3 million from $22.9 million for the prior year
period. R&D expenses increased primarily due to the timing of
our clinical research programs. We expect our R&D expenses to
vary from quarter to quarter, primarily due to the timing of our
clinical development activities.
General and Administrative (G&A) Expenses:
For the third quarter of 2023, G&A expenses decreased to
$7.1 million from $7.5 million for the prior year period.
G&A expenses decreased reflecting Prelude’s continued careful
management of its G&A expenses.
Net Loss: For the three months ended
September 30, 2023, net loss was $30.6 million, or $0.45 per
share compared to $30.0 million, or $0.63 per share, for the
prior year period. Included in the net loss for the quarter ended
September 30, 2023, was $6.7 million
of non-cash expense related to the impact of expensing
share-based payments, including employee stock options, as compared
to $6.4 million for the same period in 2022.
About Prelude Therapeutics
Prelude Therapeutics is a clinical-stage precision oncology
company developing innovative drug candidates targeting critical
cancer cell pathways. The Company’s diverse pipeline is comprised
of highly differentiated, potentially best-in-class proprietary
small molecule compounds aimed at addressing clinically validated
pathways for cancers with selectable underserved patients.
Prelude’s pipeline includes three candidates currently in clinical
development: PRT3789 an IV administered, potent and highly
selective SMARCA2 degrader, PRT2527, a potent and highly selective
CDK9 inhibitor, PRT3645 a next generation CDK4/6 inhibitor, and a
preclinical oral candidate targeting SMARCA2. For more information,
visit our website and follow us on LinkedIn.
Cautionary Note Regarding
Forward-Looking Statements
This press release contains forward-looking
statements within the meaning of the "safe harbor" provisions of
the Private Securities Litigation Reform Act of 1995, including,
but not limited to, anticipated discovery, preclinical and clinical
development activities for Prelude’s product candidates, the
potential safety, efficacy, benefits and addressable market for
Prelude’s product candidates, the expected timeline for
proof-of-concept data and clinical trial results for Prelude’s
product candidates, the sufficiency of Prelude’s cash runway into
2026, and Prelude’s planned prioritization of its SMARCA2 degrader
molecule and CDK9 inhibitor programs in the near-term. All
statements other than statements of historical fact are statements
that could be deemed forward-looking statements. Although Prelude
believes that the expectations reflected in such forward-looking
statements are reasonable, Prelude cannot guarantee future events,
results, actions, levels of activity, performance or achievements,
and the timing and results of biotechnology development and
potential regulatory approval is inherently uncertain.
Forward-looking statements are subject to risks and uncertainties
that may cause Prelude's actual activities or results to differ
significantly from those expressed in any forward-looking
statement, including risks and uncertainties related to Prelude's
ability to advance its product candidates, the receipt and timing
of potential regulatory designations, approvals and
commercialization of product candidates, clinical trial sites and
our ability to enroll eligible patients, supply chain and
manufacturing facilities, Prelude’s ability to maintain and
recognize the benefits of certain designations received by product
candidates, the timing and results of preclinical and clinical
trials, Prelude's ability to fund development activities and
achieve development goals, Prelude's ability to protect
intellectual property, and other risks and uncertainties described
under the heading "Risk Factors" in Prelude’s Annual Report on Form
10-K for the year ended December 31, 2022, its Quarterly Reports on
Form 10-Q and other documents that Prelude files from time to time
with the Securities and Exchange Commission. These forward-looking
statements speak only as of the date of this press release, and
Prelude undertakes no obligation to revise or update any
forward-looking statements to reflect events or circumstances after
the date hereof.
Investor Contact:Lindsey TrickettVice
President, Investor
Relations240.543.7970ltrickett@preludetx.com
Media Contact:Helen ShikShik Communications
617.510.4373Helen@ShikCommunications.com
|
|
PRELUDE THERAPEUTICS
INCORPORATEDSTATEMENTS OF OPERATIONS AND
COMPREHENSIVE LOSS(UNAUDITED) |
|
|
|
|
|
Three Months Ended September 30, |
|
(in thousands, except
share and per share data) |
|
2023 |
|
|
2022 |
|
Operating expenses: |
|
|
|
|
|
|
Research and development |
|
$ |
26,261 |
|
|
$ |
22,889 |
|
General and administrative |
|
|
7,124 |
|
|
|
7,517 |
|
Total operating expenses |
|
|
33,385 |
|
|
|
30,406 |
|
Loss from operations |
|
|
(33,385 |
) |
|
|
(30,406 |
) |
Other income, net |
|
|
2,777 |
|
|
|
448 |
|
Net loss |
|
$ |
(30,608 |
) |
|
$ |
(29,958 |
) |
Per share information: |
|
|
|
|
|
|
Net loss per share of common
stock, basic and diluted |
|
$ |
(0.45 |
) |
|
$ |
(0.63 |
) |
Weighted average common shares
outstanding, basic and diluted |
|
|
67,639,993 |
|
|
|
47,449,811 |
|
Comprehensive loss: |
|
|
|
|
|
|
Net loss |
|
$ |
(30,608 |
) |
|
$ |
(29,958 |
) |
Unrealized (loss) gain on marketable securities, net of tax |
|
|
106 |
|
|
|
(69 |
) |
Comprehensive loss |
|
$ |
(30,502 |
) |
|
$ |
(30,027 |
) |
|
|
PRELUDE THERAPEUTICS INCORPORATEDBALANCE
SHEETS(UNAUDITED) |
|
|
|
(in thousands, except
share data) |
|
September 30,2023 |
|
|
December 31,2022 |
|
Assets |
|
|
|
|
|
|
Current assets: |
|
|
|
|
|
|
Cash and cash equivalents |
|
$ |
15,896 |
|
|
$ |
30,605 |
|
Marketable securities |
|
|
214,610 |
|
|
|
171,123 |
|
Prepaid expenses and other current assets |
|
|
4,410 |
|
|
|
2,652 |
|
Total current assets |
|
|
234,916 |
|
|
|
204,380 |
|
Restricted cash |
|
|
4,044 |
|
|
|
4,044 |
|
Property and equipment,
net |
|
|
6,618 |
|
|
|
4,908 |
|
Right-of-use asset |
|
|
464 |
|
|
|
1,792 |
|
Prepaid expenses and other
non-current assets |
|
|
12,469 |
|
|
|
5,376 |
|
Total assets |
|
$ |
258,511 |
|
|
$ |
220,500 |
|
Liabilities and
stockholders’ equity |
|
|
|
|
|
|
Current liabilities: |
|
|
|
|
|
|
Accounts payable |
|
$ |
5,170 |
|
|
$ |
6,777 |
|
Accrued expenses and other current liabilities |
|
|
11,248 |
|
|
|
13,093 |
|
Operating lease liability |
|
|
475 |
|
|
|
1,832 |
|
Total current liabilities |
|
|
16,893 |
|
|
|
21,702 |
|
Other liabilities |
|
|
3,361 |
|
|
|
3,361 |
|
Total liabilities |
|
|
20,254 |
|
|
|
25,063 |
|
Commitments |
|
|
|
|
|
|
Stockholders’ equity: |
|
|
|
|
|
|
Voting common stock, $0.0001 par value: 487,149,741 shares
authorized; 41,965,472 and 36,496,994 shares issued and outstanding
at September 30, 2023 and December 31, 2022, respectively |
|
|
4 |
|
|
|
4 |
|
Non-voting common stock, $0.0001 par value: 12,850,259 shares
authorized; 12,850,259 and 11,402,037 shares issued and outstanding
at September 30, 2023 and December 31, 2022, respectively |
|
|
1 |
|
|
|
1 |
|
Additional paid-in capital |
|
|
662,172 |
|
|
|
531,682 |
|
Accumulated other comprehensive loss |
|
|
(605 |
) |
|
|
(1,692 |
) |
Accumulated deficit |
|
|
(423,315 |
) |
|
|
(334,558 |
) |
Total stockholders’ equity |
|
|
238,257 |
|
|
|
195,437 |
|
Total liabilities and stockholders’ equity |
|
$ |
258,511 |
|
|
$ |
220,500 |
|
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