Augment Therapeutics

Executive Summary

Augment Therapeutics engineers precision prodrugs.

Many widely used drugs are limited not by what they do, but by how they are activated or tolerated in the body. We redesign that chemistry, so the active drug is released predictably — reliably, and where it is needed.

Our BINARS™ platform (Built-In Nucleophile-Assisted Release System) is a family of self-immolative linkers that release a drug without depending on enzymes. Our lead candidate, AT-005 (E-Irinotecan), releases 100% of its active metabolite SN-38 in human plasma within 15 minutes; irinotecan itself releases none under the same conditions. Our pipeline also includes AT-002 (E-Naproxen) and AT-003 (E-Aspirin), gastric-sparing prodrugs with granted patents in the United States, Canada and India.

Because each candidate delivers an already-approved active moiety, our programs are suited to the FDA’s 505(b)(2) pathway — a faster, less costly route to approval than a full NDA, with substantially reduced clinical trial requirements

THE COMPANY AND TEAM

Augment Therapeutics is headquartered in Lake Forest, California, USA and in Hyderabad, Telangana State, India. The co-founders of the US Entity are Dr. Apparao Satyam, PhD (US Citizen), Dr. Larry Kauvar, PhD (US Citizen), Dr. Vidyasagar Vuligonda, PhD (US Citizen) and Dr. Somesh Sharma, PhD (US Citizen). The co-founders/shareholders of the Indian Entity are Mrs. Veeraveni Baddireddi (Indian citizen & Co-founder) and Dr. Apparao Satyam, PhD (US citizen, OCI & Co-founder), A PhD Pharmacologist (Indian Citizen & Shareholder), A Clinical Research Physician, MD (Indian Citizen & Shareholder) and Mr. Harmeet Singh Lamba, PGD (IIFT) (Indian Citizen & Shareholder).

Augment Scientific Team – Responsible for chemistry, preclinical and clinical research work

Dr. Apparao Satyam, PhD (US Citizen & OCI)
CEO, CSO and Co-founder of both the entities of Augment Therapeutics
35+ Years of drug discovery experience in both Indian and US Pharma industries
Sole inventor of our lead assets and BINARS™ platform

Dr. Vidyasagar Vuligonda (US citizen)
35+ years of experience in small molecule drug design and product development

Confidential Team Members:
PhD Pharmacologist (Indian Citizen)
20+ Years of experience in preclinical research

Clinical Research Physician, MD (Indian Citizen)
20+ Years of experience in clinical research

Augment Scientific Team – Responsible for dealings with US FDA on regulatory affairs

Dr. Somesh Sharma, PhD (US citizen)
40+ Years of drug discovery experience in both Indian and US Pharma industry

Dr. Larry Kauvar, PhD (US citizen)
40+ Years of drug discovery experience in US Pharma industry

Mr. Harmeet Singh Lamba, B. Pharm (BITS, Pilani), PGD (IIFT) (Indian Citizen)
30+ Years experience in Indian Pharma Industry and Expertise in APIs for Indian and global markets

A regulatory consultant/consulting agency to be hired.

Administrative Team –
Responsible for managing Admin & Finance Departments

Mrs. Veeraveni Baddireddi, MMS (Finance) (Indian Citizen)
Co-founder & Managing Director at Augment Therapeutics Pvt Ltd (INDIA)

Auditor: Mrs. Radhika Vunnam,
Chartered Accountant, Hyderabad, India

Primary Focus: Lead Oncology Asset

AT-005 (E-Irinotecan) — a novel water-soluble prodrug of SN-38

Irinotecan (Camptosar) is on the WHO List of Essential Medicines and is used to treat metastatic colorectal cancer, small cell lung cancer, and — in combination with folinic acid — pancreatic cancer. Despite $9.2B in annual global sales, irinotecan has two distinct pharmacological flaws that have persisted for over 30 years, and no approved drug has fixed them.

Flaw 1 — Grossly inefficient and unpredictable bioactivation. Irinotecan is itself a water-soluble prodrug of SN-38, a highly potent camptothecin analogue, but only 2–8% of each administered dose converts to active SN-38 in humans. SN-38 release depends on limited hepatic carboxylesterase enzymes (CES1/CES2), producing suboptimal and highly variable tumour drug exposure across patients.

Flaw 2 — Highly variable SN-38 clearance causing severe toxicities. The SN-38 that is formed is cleared through UGT1A1-mediated glucuronidation, a process that varies dramatically across patients due to UGT1A1 genetic polymorphisms. Patients with reduced UGT1A1 activity accumulate SN-38 systemically, causing severe, life-threatening toxicities including Grade 3–4 diarrhoea and neutropenia — occurring in more than 30% of patients even with current UGT1A1 pharmacogenomic dose optimisation, and forming the basis of irinotecan’s FDA Black Box Warning.

The unpredictability of Flaw 1 compounds the unpredictability of Flaw 2, making genuinely actionable precision dosing impossible with irinotecan in its current form.

Our solution. To overcome Flaw 1, we have discovered AT-005 (E-Irinotecan), a new water-soluble prodrug of SN-38 built on our proprietary BINARS™ (Built-In Nucleophile-Assisted Release System) self-immolative linker, which is pre-oriented for spontaneous intramolecular cyclisation at physiological pH (7.4) to release SN-38. In our in vitro study, AT-005 released 100% of its SN-38 in human plasma within 15 minutes under physiologically relevant conditions (pH 7.4, 37 °C). AT-005 therefore does not depend on liver carboxylesterases to release SN-38.

High potential for UGT1A1-genotype-guided precision dosing. Because AT-005 controls only the SN-38 release step and does not alter how SN-38 is cleared, it eliminates Flaw 1 entirely and leaves UGT1A1 genotype as the sole remaining pharmacokinetic variable. UGT1A1 genotyping is already an FDA-approved test and is therefore immediately actionable — enabling, for the first time, genuinely actionable genotype-guided precision dosing for an irinotecan-equivalent therapy.

Published PK–PD context. It is well established in the clinical literature on irinotecan that plasma AUC of irinotecan and SN-38 increase proportionally with dose, that SN-38 levels achieved in humans are roughly 100-fold lower than corresponding irinotecan levels (highly significant, since SN-38 is 100- to 1,000-fold more cytotoxic than irinotecan), and that irinotecan/SN-38 AUC correlates with the severity of leuko-neutropenia and diarrhoea. These relationships, established for irinotecan, underscore why better control of SN-38 exposure matters clinically. To be clear: we have not determined or reported AUC data comparing AT-005 to irinotecan. Our preclinical data to date consist of the in vitro human plasma release study and a single-timepoint plasma SN-38 comparison in mice, described below. A full AUC comparison is part of our planned preclinical programme.

Reduced off-target toxicity. Because AT-005 releases SN-38 at physiological pH without enzymatic conversion, it avoids the off-target, irinotecan-specific toxicities (such as acute cholinergic effects) that arise from the intact parent drug. Clinical dose optimisation for AT-005 therefore needs to account only for the well-characterised toxicities associated with SN-38 exposure — the same toxicities that UGT1A1 pharmacogenomic testing is already designed to help manage.

Supporting studies. Although both irinotecan and AT-005 are water-soluble prodrugs of SN-38 with a stable tert-urethane linkage, they release SN-38 to very different extents:

In vitro: In human plasma at pH 7.4 and 37 °C, AT-005 released 100% of its SN-38 within 15 minutes, whereas irinotecan released no detectable SN-38 after 2 hours — confirming that, unlike irinotecan, SN-38 release from AT-005 does not depend on carboxylesterase enzymes.

In vivo (PK): Following equimolar intravenous administration in mice, irinotecan produced approximately 1,200 ng/mL plasma SN-38 at 2 minutes, while AT-005 produced approximately 2,500 ng/mL. Rodents express substantially higher hepatic carboxylesterase activity than humans — reported at 10–100× — so this mouse model favours irinotecan relative to clinical conditions, and the 2.1-fold result understates the expected human advantage. Confirmatory studies in species with human-like carboxylesterase expression are planned.

Competitive landscape. AT-005 stands apart from other attempts to improve on irinotecan. Onivyde® (Ipsen), a liposomal irinotecan, still inherits irinotecan’s underlying carboxylesterase-dependent activation. Trodelvy® (Gilead), an SN-38 antibody-drug conjugate, achieves near-complete SN-38 payload delivery but uses a hydrolysable carbonate linker with a reported half-life of approximately 20 hours in circulation. AT-005 depends on neither enzymatic activation nor a comparably fast-hydrolysing linker.

IP status. A non-provisional patent application covering AT-005 and the BINARS™ linker platform was filed with the Indian Patent Office on 9 July 2026. Accelerated examination has been requested as a DPIIT-recognised Indian startup under the Startup India SIPP Scheme. Corresponding PCT and US national-phase applications are planned. The platform has further applications described in our patent filings; details are available under confidentiality.

Secondary Focus: Pipeline Anti-inflammatory Assets
Beyond our primary oncology asset AT-005 (built on our BINARS™ self-immolative linker platform), we have also developed two additional, earlier-stage “Enhanced Medicines” using a novel enzyme-independent acid-labile prodrug technology, as described below:

Pipeline Asset 1: AT-002 (E-Naproxen) — Development of NO-Naproxen as an “Enhanced” version of the widely used pain and arthritis medicine naproxen through the 505(b)(2) regulatory route.

Generic naproxen, a non-steroidal anti-inflammatory drug (NSAID), is widely used for the treatment of pain and other inflammatory conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, gout, menstrual cramps, etc.

However, like most other NSAIDs, long-term use of naproxen is associated with severe gastrointestinal (GI) lesions, ulcers, and bleeding. Additionally, recent studies have shown an increased risk of major cardiovascular events such as rise in blood pressure within 30 days of an NSAID use. To reduce the NSAID-induced GI complications, a few approaches such as co-medication with acid suppressants such as proton pump inhibitors (PPIs) and prostaglandin analogues are currently used. However, long term use of PPIs has shown many side effects. In the mid-1990s, COX-2 selective inhibitors were introduced as gastro-protective NSAIDs, and they became very successful within a short period of time. However, some of these COX-2 inhibitors were withdrawn from market due to their inherent cardiovascular risk. This has created a real unmet medical need for safer versions of NSAIDs which do not cause the said GI complications. Recently, a new class of nitric oxide (NO) releasing prodrugs of NSAIDs or simply NO-NSAIDs, are being studied as potentially gastro-protective NSAIDs. These NO-NSAIDs mostly retain the anti-inflammatory properties of parent NSAID, but they also exhibit significantly reduced GI toxicity, which is attributable to the beneficial effects of NO released from these compounds.

We have now discovered a novel NO-Naproxen prodrug (2A/P7133/AT-002), which is aptly named as “Enhanced Naproxen” or “E-Naproxen”, by using a novel enzyme-independent platform linker technology and our E-Naproxen:

Exhibited statistically significant superior bioavailability than naproxen in rats [See Figure 1 showing comparison of bioavailability data among naproxen and its prodrugs 2A (P7133/AT-002), 2B (P7135), 2C (P7134) and 2D (P7132)];
Protected experimental rats from NSAID-induced gastric damage, which could be due to the beneficial effects of NO released from this NO-NSAID (See Figures S2 and 9).
May show anti-hypertensive potential due to release of NO, which is a known vasodilator and regulator of blood pressure.

Thus, as shown in Figure 1, our E-Naproxen (2A/AT-002) has exhibited statistically significant increase in bioavailability (AUC: 272.60 ± 8.50 mg*h/ml, **p <0.01 vs naproxen) over its parent drug naproxen [AUC: 207.80 ± 18.20 mg*h/ ml, **p <0.01 vs NO-Naproxen (2A/AT-002)]. To our knowledge, this is the first report of a naproxen prodrug having a statistically significant increase in bioavailability than its parent drug naproxen.

Interestingly, as shown in Figure 1, our E-Naproxen (2A/AT-002) has also exhibited a more controlled or sustained release of naproxen and maintained a higher plasma drug concentration over a longer period (>30 micrograms/ml plasma drug concentration up to 6 hrs. duration) when compared to that of naproxen at equimolar doses. Our E-Naproxen is therefore expected to offer better pain relief over a longer period than the parent drug naproxen.

Figure 2 shows the comparative PK data of E-Naproxen (AT-002), Naproxen, and two competitor naproxen prodrugs Naproxcinod (Nicox, Sophia Antipolis, Valbonne, France), and LT-NS001 (Logical Therapeutics, Waltham, MA) and naproxen. Both Naproxcinod and LT-NS001 have been evaluated in Phase 2 clinical trials in arthritis patients and their structures are also shown in Figure 2. Interestingly, AT-002 uptake is substantially faster than the other two prodrugs, with total exposure [AUC (area under the curve)] markedly better for AT-002 than both the comparators’ products. AT-002’s better bioavailability is due to its unique acid-labile “acyl-acetal” linkage that breaks down to release naproxen quantitatively under the acidic conditions in the stomach. By contrast, naproxcinod and LT-NS001 are simple ester prodrugs and depend on enzymatic cleavage to release naproxen in vivo.

Gastric tolerance study. Since AT-002 is expected to release free naproxen quantitatively in the acidic stomach following oral administration, we have evaluated the ulcerogenic potential after acute dosing of naproxen sodium (109.52 mg/kg, which is equimolar to 100 mg/kg naproxen) and AT-002 (138.67 mg/kg, which is equimolar to 100 mg/kg naproxen). 5 h after administration of test articles to overnight fasted rats (5 per group), the animals were sacrificed and the stomachs dissected, perfused with 2% formalin (10 ml), and a large curvature excised for imaging using a stereomicroscope attached to a digital camera (Stemi 2000; Zeiss, Germany), as shown in Figure 3. The severity of the mucosal damage was assessed by the size of the ulcer lesions using Image Pro Plus software (Media Cybernetics, Rockville, MD) to quantify the hemorrhagic/ulcer lesions in mm² as shown in Figure 4. The calculated gastric lesion & ulcer area was 39 ± 20 mm² for AT-002 vs 580 ± 80 mm² for naproxen (p<0.001). These results demonstrate that the animals treated with AT-002 had only minimal GI damage in sharp contrast to the severe hemorrhagic lesions, ulcers and bleeding in rats administered with naproxen (i.e., naproxen sodium) at equimolar doses.

Strong Possibility for Drug Development and Approval through 505(b)(2) NDA route: We strongly believe that our E-Naproxen (P7133/A2/AT-002), with its above-mentioned competitively advantageous properties over naproxen, is an ideal candidate for development through 505(b)(2) regulatory route, which is the least expensive shorter route for drug approval.

Competitive Advantages and Market Impact: The above-mentioned positive attributes make the E-Naproxen (P7133/2A/AT-002) competitively advantageous over naproxen. We therefore believe that this E-Naproxen could represent a novel “First-in-the-Class” of “Safer NSAID” for the treatment of arthritic pain and a host of inflammatory diseases. Thus, this E-Naproxen, when it is approved, has the greatest potential to create disruption in NSAIDs market by grabbing significant market share from naproxen and other approved NSAIDs and has the potential to become a BLOCKBUSTER drug within a short period of its introduction to market.

IP/Patents: We have already obtained US, Canadian and Indian patents covering our E-Naproxen [See US 9,844,599, (Dec 19, 2017), CA 2 897 571 C (Dec 18, 2018) and IN 345054 (Aug 25, 2020)]. We have also published this work [See Bioorganic & Medicinal Chemistry Letters, 2014, 24, 5587-92].

Pipeline Asset 2: AT-003 (E-Aspirin) — NO-Aspirin as an “Enhanced” version of the widely used wonder drug aspirin:

Aspirin has been in use as an anti-inflammatory and anti-pyretic drug for over 100 years. Recently, aspirin is also widely used for the treatment of cardiovascular diseases. However, significant number of aspirin users suffer from NSAID-induced severe gastrointestinal lesions, bleeding and ulcers. Currently, proton pump inhibitors are used in combination with aspirin to reduce NSAID-induced GI damage. However, long-term use of PPIs leads to many side effects such as osteoporotic fractures. So, there is an immediate unmet medical need for safer versions of aspirin. As a solution, we have now invented an “Enhanced Aspirin” or “E-Aspirin” or “AT-003”, which has shown comparable oral bioavailability and antiplatelet activity (i.e., TXB2 inhibition) to those of aspirin but it did not cause any significant NSAID-induced gastric lesions, bleeding, and ulcers. Thus, our E-Aspirin (AT-003) represents a First-in-Class of potentially “Safe Aspirin” for the treatment of cardiovascular disorders and is an ideal candidate for development through the least expensive 505(b)(2) regulatory route.

IP/Patents: We have already obtained US, Canadian and Indian patents covering our E-Aspirin [See US 9,844,599, (Dec 19, 2017), CA 2 897 571 C (Dec 18, 2018) and IN 345054 (Aug 25, 2020)]. We have also published this work [See Bioorganic & Medicinal Chemistry Letters, 2014, 24, 5587-92].

Exclusive Licensing of Proprietary Novel Linker Technologies: An exclusive license agreement to the technology has been secured from Piramal Enterprises, Mumbai, India.

For further Information, please contact:

Dr. Apparao Satyam, PhD.
CEO & CSO, Augment Therapeutics. Inc. | Augment Therapeutics Private Limited
The US Entity: Lake Forest, CA 92630, USA
The Indian Entity: Hyderabad-500089, India
Email: apparao.satyam@augmenttherapeutics.com