LADRX CORPORATION Overview
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LADR Drug Discovery Platform and Centurion
Centurion's LADR™ (Linker Activated Drug Release) technology platform is a discovery engine combining our expertise in linker chemistry and albumin biology to create a pipeline of anti-cancer molecules that will avoid unacceptable systemic toxicity while delivering highly potent agents directly to the tumor. Centurion has created a "toolbox" of linker technologies that are designed to significantly increase the therapeutic index of ultra-high potency drugs (10-1,000 times more potent than traditional cytotoxins) by controlling the release of the drug payloads and improving drug-like properties.
Centurion's efforts were focused on two classes of ultra-high potency albumin-binding drug conjugates. These drug conjugates combine the proprietary LADR™ linkers with novel derivatives of the auristatin and maytansinoid drug classes. These payloads historically have required a targeting antibody for successful administration to humans. These drug conjugates eliminate the need for a targeting antibody and provide a small molecule therapeutic option with potential broader applicability.
Centurion's postulated mechanism of action for the albumin-binding drug conjugates is as follows:
? after administration, the linker portion of the drug conjugate forms a rapid
and specific covalent bond to the cysteine-34 position of circulating albumin;
? circulating albumin preferentially accumulates at the tumors, bypassing
concentration in other non-tumor sites, including the heart, liver and
gastrointestinal tract due to a mechanism called "Enhanced Permeability and
Retention";
? once localized at the tumor, the acid-sensitive linker is cleaved due to the
specific conditions within the tumor and in the tumor microenvironment; and
? free active drug is then released.
Centurion's novel companion diagnostic, ACDx™ (albumin companion diagnostic), was developed to identify patients with cancer who are most likely to benefit from treatment with the four LADR lead assets.
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Aldoxorubicin
Until
On
Aldoxorubicin is a conjugate of the commonly prescribed cytotoxin agent doxorubicin that binds to circulating albumin in the bloodstream and is believed to concentrate the drug at the site of the tumor. Aldoxorubicin has been tested in over 600 patients with various types of cancer. Specifically, it is comprised of (6-maleimidocaproyl) hydrazine, an acid-sensitive molecule that is conjugated to doxorubicin. The initial indication for aldoxorubicin is for patients with advanced soft tissue sarcomas (STS). ImmunityBio lists a randomized Phase 2 and a randomized Phase 3 study, as well as an aldoxorubicin and ifosfamide Phase 1/2 study in its solid tumor platform and is currently reviewing options in STS.
Aldoxorubicin has received Orphan Drug Designation (ODD) by the
In addition to STS, ImmunityBio has expanded aldoxorubicin's use by combining it with immunotherapies and cell-based treatments and is currently in late-stage clinical development in advanced and metastatic pancreatic cancer, in glioblastoma, and in triple negative breast cancer. ImmunityBio has initiated a phase 2 registrational-intent study in metastatic pancreatic cancer.
Molecular Chaperone Assets (Orphazyme)
In 2011,
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Current Business Strategy for LADR™ Platform
Currently, the Company and Centurion are working on identifying partnership opportunities for LADR™ ultra-high potency drug conjugates and their albumin companion diagnostic, although no partnerships or other sources of financing have become available after over two years of effort. The Company has no plans to conduct further research and development on LADR and its companion diagnostic, but continue to focus on identifying these partnership and financing opportunities
Critical Accounting Policies and Estimates
Management's discussion and analysis of our financial condition and results of
operations are based on our financial statements, which have been prepared in
accordance with accounting principles generally accepted in the
We base our estimates on historical experience and on various other assumptions that are believed to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ materially from these estimates under different assumptions or conditions.
Our significant accounting policies are summarized in Note 2 to our financial
statements contained in our Annual Report on Form 10-K for the year ended
Stock-Based Compensation
The Company accounts for share-based awards to employees and nonemployees directors and consultants in accordance with the provisions of ASC 718, Compensation-Stock Compensation., and under the recently issued guidance following FASB's pronouncement, ASU 2018-07, Compensation-Stock Compensation (Topic 718): Improvements to Nonemployee Share-Based Payment Accounting. Under ASC 718, and applicable updates adopted, share-based awards are valued at fair value on the date of grant and that fair value is recognized over the requisite service, or vesting, period. The Company values its equity awards using the Black-Scholes option pricing model, and accounts for forfeitures when they occur.
Basic and Diluted Net Loss per Common Share
Basic and diluted net loss per common share is computed based on the
weighted-average number of common shares outstanding. Common share equivalents
(which consist of options, warrants and restricted stock) are excluded from the
computation of diluted net loss per common share where the effect would be
anti-dilutive. Common share equivalents that could potentially dilute net loss
per share in the future, and which were excluded from the computation of diluted
loss per share, totaled 3.2 million shares for the three-month period ended
Liquidity and Capital Resources
We have relied primarily upon proceeds from sales of our equity securities and the exercise of options and warrants, and to a much lesser extent upon payments from our strategic partners and licensees, to generate funds needed to finance our business and operations.
At
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recorded a net loss in the three-month period ended
We purchased no fixed assets in the period ended
There were no financing transactions in either three month-periods ended
We continue to evaluate potential future sources of capital, as we do not currently have commitments from any third parties to provide us with additional capital and we may not be able to obtain future financing on favorable terms, or at all. The results of our technology licensing efforts and the actual proceeds of any fund-raising activities will determine our ongoing ability to operate as a going concern. Our ability to obtain future financings through joint ventures, product licensing arrangements, royalty sales, equity financings, grants or otherwise is subject to market conditions and our ability to identify parties that are willing and able to enter into such arrangements on terms that are satisfactory to us. Depending upon the outcome of our fundraising efforts, the accompanying financial information may not necessarily be indicative of our future financial condition. Failure to obtain adequate financing would adversely affect our ability to operate as a going concern.
There can be no assurance that we will be able to generate revenues from our product candidates and become profitable. Even if we become profitable, we may not be able to sustain that profitability.
Results of Operations
We recorded a net loss of approximately
We recognized no licensing revenue in the three-month periods ended
General and Administrative Expenses
Three-Month Period Ended
March 31,
2021 2020
(In thousands)
General and administrative expenses $ 1,277 $ 1,133
Employee stock, and stock option expense - 87
Depreciation and amortization 3 6
$ 1,280 $ 1,226 General and administrative expenses include all administrative salaries and
general corporate expenses, including legal expenses. Our general and
administrative expenses, excluding stock option expense, non-cash expenses and
depreciation and amortization, were
Depreciation and Amortization
Depreciation expense reflects the depreciation of our equipment and furnishings.
18 Interest Income and Expense
Interest income was approximately
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