LSLP CREST TB Formulation Programme is a Kenya-led proof-of-concept initiative to develop and test a proprietary plant-derived oral drug-delivery platform for established first-line anti-tuberculosis medicines. The programme does not propose a new active pharmaceutical ingredient. It asks whether changing how an existing medicine is carried and released can create a scientifically credible pathway toward more controlled exposure while preserving antimicrobial activity.

This is a Kenyan original. The formulation concept was conceived in Nairobi by a Kenyan founder, and the platform is deliberately built on zein — a protein extracted from maize, one of Kenya's staple crops — so the core input can ultimately be grown, milled and processed in Kenya rather than imported. The programme's ambition is for this to become the first TB nanomedicine candidate conceived, developed and manufactured in Kenya. That origin claim will be substantiated with documentary evidence — a dated invention record, patent filings through the Kenya Industrial Property Institute and international equivalents, and the full trial record — before it is presented to any funder.

The central hypothesis is that a protected oral formulation can be engineered to modify drug-release behaviour in laboratory testing and may, subject to later preclinical and clinical validation, reduce sharp peak exposure associated with immediate-release dosing. Reduced hepatotoxicity, improved tolerability, adherence or clinical outcomes are not established claims at this stage.

The proposed proof of concept will progress through formulation screening, physicochemical characterisation, release testing under simulated gastrointestinal conditions, stability assessment and confirmation of retained antimycobacterial activity. A staged go/no-go framework will prevent advancement unless the candidate demonstrates reproducibility, acceptable loading and stability, a defensible release profile and preserved biological function.

By programme completion, LSLP CREST intends to produce a lead-candidate decision, a reproducible laboratory method, a nonclinical evidence package, a regulatory and intellectual-property roadmap, a preliminary manufacturing-transfer plan and a costed next-stage development strategy. The exact duration, requested budget, funder and formal implementation partners remain to be confirmed.

This section will be tailored to the selected funding opportunity. In its current funder-neutral form, the programme aligns with common priorities in translational global-health research: improving the delivery of established essential medicines, building locally led pharmaceutical research capability, strengthening product-development pathways in Africa and generating decision-grade evidence before expensive scale-up.

Tuberculosis remains a major cause of preventable illness and death. Effective first-line medicines exist, yet treatment requires sustained exposure over time and can be complicated by adverse effects. Drug-induced liver injury is a clinically important risk associated with several anti-TB regimens. When toxicity is suspected or confirmed, treatment may be interrupted, changed or monitored more intensively, creating consequences for patients and health systems.

The proposed innovation addresses a formulation question rather than a drug-discovery question: can an existing anti-TB medicine be delivered through a protected oral system that produces a more controlled laboratory release profile while retaining its intended biological activity? If supported by evidence, this could justify later studies of pharmacokinetics, tolerability and clinical utility.

3.1 Why the Kenyan setting matters

Kenya combines a continuing TB burden with research institutions, pharmaceutical capability and public-health infrastructure that can support locally relevant product development. Designing for local analytical capacity, realistic supply chains and eventual manufacturing transfer may reduce the distance between laboratory evidence and an accessible product.

The setting is also the origin. The platform's core input — zein — is a protein extracted from maize, a crop Kenya grows at industrial scale. Turning a Kenyan crop into a Kenyan medicine is a supply-chain story a reviewer can verify on the ground, and no Kenyan-origin TB nanomedicine candidate has yet been carried through this route; being first is part of the scientific and national value the programme is built to demonstrate.

3.2 Intended population and use context

The long-term intended users are people receiving anti-TB therapy who may benefit from a safe, effective and practical oral formulation. No patient use is proposed in the initial laboratory proof of concept. Paediatric or adherence-sensitive dosage forms may be considered later only after stability, dosing, acceptability and regulatory requirements are understood.

3.3 Why LSLP CREST is positioned to lead

LSLP CREST brings a locally anchored product-development proposition focused on moving published scientific principles toward a controlled, testable and potentially manufacturable candidate. Institutional claims, prior projects and named personnel must be documented before submission.

4.1 Innovation hypothesis

A proprietary plant-derived oral carrier can be optimised to protect an established anti-TB medicine during early gastrointestinal transit and support a more gradual release profile under later-stage gastrointestinal conditions. The resulting exposure profile may justify subsequent evaluation of pharmacokinetic and tolerability benefits.

4.2 Innovation components

• An established anti-TB active ingredient selected through a documented development rationale.
• A proprietary plant-derived carrier and controlled encapsulation process.
• A candidate oral dosage form chosen through stability, usability and manufacturability evidence.
• A staged analytical package covering loading, physical properties, release behaviour and storage stability.
• Biological testing to confirm that formulation does not compromise intended antimycobacterial activity.

4.3 What is genuinely new

The proposed innovation is not the existence of the medicine or the broad scientific idea of drug encapsulation. Its potential proprietary value lies in the specific formulation window, production sequence, process controls, performance characteristics and locally executable manufacturing package generated through the research.

Origin is a further distinguishing dimension. The carrier is maize-derived and Kenya is a maize-growing country, so the programme can pursue a supply chain that runs from Kenyan grain to Kenyan medicine — a direction imported carrier systems cannot copy. A local zein sourcing and extraction study sits inside the manufacturing-translation work (Sections 10 and 11), and the Kenya-first positioning is documented, not asserted (Section 1).

4.4 Product-development strategy

Different active ingredients will not be assumed to behave identically. The programme will begin with a clearly justified lead candidate and use comparative work only where resources and scientific evidence support it. Lead selection will be data-driven.

This section states the formulation directly. The platform is a zein-protein nanoparticle carrying established first-line anti-TB actives — rifampicin, isoniazid and pyrazinamide. Zein is a hydrophobic maize prolamine that is insoluble at gastric pH and erodes under intestinal conditions, which is the physical basis for the pH-gated release profile below.

5.1 Particle architecture

Rifampicin, being hydrophobic, partitions into the zein core. Isoniazid, being hydrophilic, is held in the hydrated, surfactant-stabilised shell. A single particle therefore carries both actives with distinct release kinetics.

5.2 Critical process parameters (CPPs)

Four parameters are varied; everything else is held fixed by protocol. These bounds define the searchable design space of the engine.

5.3 Critical quality attributes (CQAs) and acceptance targets

5.4 pH-gated release mechanism

5.5 Optimiser output — current best parameter sets

The engine runs 5,000 Monte-Carlo sweeps of the bounded design space per drug, predicts the three CQAs from the response surface, and scores each candidate as EE/100 − 0.5 × relative size error − 0.5 × PDI excess. Targeting a 180 nm particle, the current optimum for each active is:

A tighter 140 nm target for rifampicin converges on 7.59 mg/mL zein, 1.48 % w/v surfactant, a 0.136 drug:zein ratio at pH 7.10, giving 140.0 nm, PDI 0.193 and 58.2 % EE — the trade-off between small particles and high loading is explicit and quantified.

5.6 Expected dissolution curves

5.7 Alternative strategies under evaluation

5.8 The optimisation loop

The executable engine — synthetic dataset generator, response-surface predictor, fitness function and Monte-Carlo optimiser, built on NumPy and pandas — is attached to this proposal as formulation_agent.py. A private AI lab assistant that accepts raw bench observations and returns specific corrective instructions runs at /lab behind authentication.

5.9 Step-by-step bench protocol

The lead candidate is produced by anti-solvent precipitation. The sequence below is written at the batch scale used for characterisation (100 mL aqueous phase) and uses the optimiser's current rifampicin parameter set.

1. Step 1 — Dissolve the zein — Weigh zein to give 12.76 mg/mL in the organic phase and dissolve in 70–80 % aqueous ethanol. Stir at 600 RPM until the solution is clear and free of visible protein flecks.
2. Step 2 — Add the active — Add rifampicin at a drug-to-zein ratio of 0.171 w/w. Protect from light and stir until fully dissolved. Do not heat above 40 °C.
3. Step 3 — Prepare the aqueous phase — Prepare 100 mL of aqueous surfactant at 1.15 % w/v and adjust to pH 6.59 using dilute acid or base. Equilibrate to the working temperature (25–40 °C).
4. Step 4 — Anti-solvent injection — Inject the organic phase into the stirring aqueous phase at a constant rate using a syringe pump, with stirring at 1000–1200 RPM. Nanoparticles form on contact as the ethanol diffuses out and the zein precipitates around the drug.
5. Step 5 — Solvent removal — Remove the ethanol by rotary evaporation under reduced pressure with the bath held at 25–40 °C. Continue until residual ethanol is below the method limit.
6. Step 6 — Wash, collect and dry — Centrifuge, discard the supernatant (retain it for the free-drug assay), resuspend in buffer, repeat once, then lyophilise with a cryoprotectant. Store the dry powder desiccated and protected from light.
7. Step 7 — Record and feed back — Enter the measured diameter, PDI and encapsulation efficiency into the lab assistant. It compares them against the predicted values and returns the next parameter adjustment.

5.10 Characterisation and release testing steps

1. Size and polydispersity — Dilute the suspension in filtered buffer and measure by dynamic light scattering at 25 °C, three runs per batch. Accept 150–220 nm with PDI ≤ 0.25.
2. Encapsulation efficiency — Separate free drug by ultrafiltration, quantify it by HPLC against a calibration curve, and calculate EE as (total − free) ÷ total. Accept above 80 %.
3. Simulated gastric release — Incubate in pH 1.2 fluid at 37 °C with agitation, sampling at 0.5, 1 and 2 h. Accept under 15 % released at 2 h.
4. Simulated intestinal release — Transfer to pH 7.4 buffer at 37 °C and sample at 4, 8, 12, 18 and 24 h. Accept at least 85 % cumulative release at 24 h.
5. Retained activity — Run a mycobacterial susceptibility assay on the formulated particles against free drug. The minimum inhibitory concentration must not be materially worse than the free drug control.
6. Stability — Hold sealed samples at 25 °C/60 % RH and 40 °C/75 % RH and repeat size, PDI, EE and assay at 1, 3 and 6 months.

A batch that fails any gate is not discarded as a loss: its measured values are logged as a new training row, the optimiser re-scores the design space, and the next batch is run at the corrected parameters.

5.11 Trial TB-01 — full report

The protocol above was executed as a three-batch replicate trial on the rifampicin lead candidate, with the engine selecting the parameters, the batches characterised against the CQA gates, and the AI lab assistant reviewing the results and setting the next experiment. This section reports that trial in full, including the gate it failed.

Trial design

Measured results

Measured dissolution profile

Two hours in simulated gastric fluid at pH 1.2, then transfer to pH 7.4 intestinal buffer at 37 °C; cumulative release referenced to encapsulated drug.

The shape is the one the platform is built for: the coating holds in acid, then releases steadily across the full day rather than in a single early spike.

Lab assistant review

The trial record was submitted to the AI lab assistant, which returned three findings. First, a design-rule flag: the chitosan shell at 20 % of zein mass is below the 25 % minimum and triggers the high gastric leak and burst release warning — a rule violation, not an observed failure, since the measured 2 h release was only 9.2 %. Second, the encapsulation shortfall (63.3 % against an 80 % target) is far larger than the batch-to-batch variability (coefficient of variation 4.1 % for EE, 5.2 % for size), so tightening reproducibility alone cannot close it. Third, process pH 6.59 sits where many chitosan grades lose protonation, which makes shell deposition inconsistent.

Corrective experiment — TB-02

The preferred starting point is 25 % chitosan at a 0.150 drug:zein ratio — the smallest departure from the conditions that already delivered the right size and release. At 80 % EE this yields roughly 1.43 mg/mL encapsulated rifampicin, essentially matching TB-01's 1.42 mg/mL, so the higher efficiency is not bought at the cost of dose.

Next steps

1. 1. Run the TB-02 shell and loading screen — Four conditions in triplicate against a TB-01 control. Advance only a condition where every independent batch exceeds 80 % EE while holding size, PDI, yield and release.
2. 2. Validate the encapsulation assay first — Distinguish particle-associated drug from unencapsulated crystals that co-sediment, and report EE, loading, yield and total drug recovery together. Without this, a procedural change can appear to raise EE without improving encapsulation.
3. 3. Fix the sources of batch variation — Standardise vessel geometry, fill volume, impeller size, injection rate and feed position, chitosan stock age and coating time, solvent-removal endpoint, and material lots. Stirring speed alone does not control mixing.
4. 4. Characterise the chitosan coating step — Record molecular weight, degree of deacetylation, dissolution acid and stock pH; measure pH before precipitation, after chitosan addition and after solvent removal. If aggregation indicates poor solubility, run a separate pH 5.5–6.0 coating screen.
5. 5. Confirm the release protocol — Verify sink conditions, sampling-volume correction and rifampicin stability in both media, so acid degradation is never mistaken for slow release.
6. 6. Add isoniazid co-encapsulation — TB-01 was rifampicin only. Co-encapsulation is tested in TB-03, comparing the polymer core–shell route against the IH2 benz-hydrazone linker route at 25–40 °C.
7. 7. Only then test the liver endpoint — Hepatocyte toxicity is a separate experimental endpoint and cannot be inferred from encapsulation and dissolution data.

5.12 Trial TB-02 — full report

TB-02 executed the corrective screen set out above: the chitosan shell was raised from 20 % to 25 % and 30 % of zein mass, the drug:zein ratio was lowered from 0.188 to 0.150 and 0.120, the coating step was moved to pH 5.7 where chitosan is reliably protonated, the encapsulation assay was revalidated by ultrafiltration with HPLC quantification, and vessel geometry, injection rate and chitosan stock age were standardised. Four conditions were run in triplicate against a repeat of the TB-01 settings as control.

Trial design

Zein was held at 11.90 mg/mL, surfactant at 0.89 % w/v, stirring at 1000 RPM and temperature at 30 °C across every arm, so the screen separates shell loading and drug loading from the rest of the process.

Measured results — means of three independent batches

C1 is the lead condition. It clears all five gates and carries 18.5 % more encapsulated rifampicin per millilitre than C2, so the gain in efficiency is not paid for in dose. Its weakness is margin: 82.4 % EE sits only 2.4 percentage points above the gate, so batch-level standard deviations must be reported before the pass is called robust. The control reproducing 64.1 % EE confirms that the improvement comes from the design changes and not from the revalidated assay.

Why the numbers moved

• Lower drug loading reduces competition for the hydrophobic domains in zein, so less rifampicin is left unincorporated.
• A heavier chitosan shell improves surface coverage and reduces drug escape during preparation and release.
• Coating at pH 5.7 keeps chitosan protonated, which makes shell deposition consistent batch to batch.
• At 30 % chitosan the coating is denser and the particles larger, so the diffusion path lengthens and release stalls short of 85 % by 24 hours — retention improves at the cost of completeness.

These are mechanistic hypotheses consistent with the data, not proven causes. TB-02 separates shell loading from drug loading, but it does not isolate the pH change from the other process corrections made at the same time.

Lead-condition dissolution profile (C1)

Only the 2 h and 24 h points are measured. The intermediate values are a planning curve; a full sampling series is required before sustained release across the whole day can be claimed.

Flags and risks carried forward

• C1 and C2 sit exactly at the 25 % shell minimum, so actual coating recovery must be measured rather than inferred from the feed ratio.
• Shell loading must always be reported as chitosan mass over zein mass, never as a percentage of total solids.
• The evidence remains rifampicin-only: it establishes neither isoniazid retention nor any liver benefit.
• Batch standard deviations, a dissolution mass balance and degradation accounting are still outstanding; a validated encapsulation assay does not validate the release measurement.

TB-03 next steps

1. 1. Confirm C1 — Repeat independent batches at the C1 settings and report individual values, standard deviations, recovery and gate margins. Keep C2 as the backup condition.
2. 2. Introduce isoniazid — Hold total drug:zein at 0.150 and replace part of the rifampicin with isoniazid at a defined therapeutic ratio, quantifying each drug's encapsulation and concentration separately.
3. 3. Test shell retention — Start at 25 % chitosan and only step up to about 27.5 % if isoniazid leaks. Both drugs must clear the encapsulation and release gates; do not default to 30 %.
4. 4. Run an IH2 feasibility arm — Fix the zein-to-IH2 ratio and hold synthesis between 25 °C and 40 °C. Treat the higher loading claim as unverified and establish identity, purity, linker cleavage and recovery of active isoniazid.
5. 5. Check stability and full release — Track size, PDI, aggregation, drug content, degradants and leakage on storage, and measure the complete sequential-pH curve with stability-indicating assays and a terminal mass balance.
6. 6. Confirm antibacterial activity — Compare the formulation against dose-matched free drug in a validated antimycobacterial assay, including blank particles as a control.
7. 7. Measure the hepatocyte response — Compare co-loaded particles, the free-drug combination, single-drug formulations and blank carrier at matched doses, using viability plus a second injury endpoint. Claim reduced toxicity only alongside retained activity.

Overall goal: To develop and evaluate a reproducible, proprietary oral delivery candidate for an established anti-TB medicine and determine whether it merits progression to advanced nonclinical development.

5.1 Core research questions

• Can a reproducible candidate be produced within a predefined formulation and process design space?
• Does the candidate remain stable under relevant short-term and accelerated conditions?
• Does it produce a differentiated and reproducible release profile in comparative laboratory testing?
• Is intended antimycobacterial activity retained after formulation?
• Which candidate offers the best balance of performance, safety rationale, manufacturability and cost?
• What evidence is required before pharmacokinetic, toxicology or clinical studies are ethically and scientifically justified?

At this stage, success is defined by decision-quality laboratory evidence—not by assumed patient benefit. Technical performance is necessary but not sufficient for progression.

6.1 Intermediary outcomes

• A documented quality-by-design formulation rationale.
• Improved local capability in formulation, analytics and product-development governance.
• A protected technical package suitable for controlled partner diligence.
• A clear go, revise or stop decision based on prespecified evidence.

7.1 Study design

The project will use a staged, laboratory-based proof-of-concept design. Candidate progression will be governed by prespecified acceptance criteria and documented decision gates. Replication, controls, blinded analysis where feasible and protocol deviations will be recorded.

7.2 Work packages

7.3 Candidate and control strategy

The protocol will specify the active ingredient, reference product or standard, unformulated control, blank-carrier control and candidate variants. Different medicines will be evaluated separately unless compatibility and analytical evidence justify a combined approach.

7.4 Sample size and replication

Technical replicates, independent batches and acceptance ranges will be set with the analytical partner after method capability is confirmed. Final sample numbers will be justified against variability, assay precision, decision thresholds and available resources rather than selected arbitrarily.

7.5 Data inputs

• Batch manufacturing records and yields.
• Loading and recovery data.
• Physical and morphological measurements.
• Release profiles and model parameters.
• Stability-indicating measurements.
• Antimycobacterial assay outputs.
• Cost, sourcing, quality and process-risk data.

7.6 Analysis

Analysis will summarise central tendency, variability, batch-to-batch reproducibility and comparative performance. Release curves will be assessed with appropriate kinetic models selected in the protocol. Inferential analyses will report effect estimates and uncertainty; statistical significance alone will not determine progression.

7.7 Quality and reproducibility

Controlled procedures, calibrated equipment, traceable materials, versioned protocols, raw-data retention and independent review will be required. Any outsourced laboratory will be assessed for relevant quality systems and method capability.

7.8 Patient and stakeholder involvement

Although the initial PoC is laboratory based, clinicians, TB-programme stakeholders and prospective users should inform the target product profile, acceptable dosage forms and future study priorities. Their involvement will not substitute for formal product testing.

7.9 Scientific and Product Advisory Committee

LSLP CREST will establish an advisory group covering TB pharmacology, formulation science, analytical chemistry, microbiology, toxicology, regulatory strategy, manufacturing, statistics, patient perspectives and intellectual property, subject to formal appointments.

8.1 Evaluation framework

The programme theory of change is: controlled research inputs → reproducible formulation process → verified laboratory performance → justified lead selection → advanced nonclinical development → potential future patient benefit.

8.2 Demonstrating formulation performance

Performance will be demonstrated through comparison with appropriate controls, independent batches and prespecified conditions. Claims will remain bounded by what the assay directly supports.

8.3 Learning cycles

Quarterly learning reviews will assess evidence, safety signals, cost, operational constraints and stakeholder feedback. Each change to the protocol or target product profile will be justified, approved and documented.

The schedule below is a provisional 24-month structure copied from the malaria proposal’s planning discipline, not a confirmed commitment. It must be reconciled with partner capacity, assay turnaround, ethics and regulatory requirements.

A detailed, quotation-backed budget will be prepared after partner scope, duration and assay requirements are confirmed. The requested amount is [TO BE CONFIRMED].

10.1 Financial viability questions

• Can critical inputs be sourced consistently at appropriate quality?
• What are the dominant cost drivers at laboratory, pilot and commercial scales?
• Can the process be transferred without equipment or control requirements that defeat affordability?
• Which partnership or licensing model supports access while preserving LSLP CREST’s rights?
• What evidence milestone creates the next credible financing event?

Sustainability depends on whether the platform can move beyond a successful experiment into a controlled process, viable supply chain and appropriate regulatory programme. Scale is therefore treated as a designed pathway with evidence gates, not as automatic replication.

11.1 Environmental footprint and responsible implementation

The programme will favour right-sized experiments, qualified regional sourcing where feasible, solvent and waste minimisation, safe disposal, shared analytical infrastructure and documented energy and material demands. Environmental choices will not compromise product quality or researcher safety.

11.2 Scale-readiness criteria

• A reproducible lead candidate and defined critical quality attributes.
• A process map with controllable critical parameters and acceptable yields.
• No unresolved supply, safety or analytical barrier that makes translation impractical.
• A preliminary regulatory classification and development pathway.
• A credible freedom-to-operate and protection strategy.
• A cost model and partner pathway for pilot production under appropriate quality standards.
• An evidence-based plan for pharmacokinetic, toxicology and eventual clinical evaluation.

11.3 A Kenyan supply chain and manufacturing pathway

• Zein is extracted from maize; Kenya mills maize at industrial scale, and the gluten-rich side streams of that milling are the natural local feedstock for a zein source.
• Where pharmaceutical-grade zein is not yet produced in Kenya, the initial programme will purchase qualified material internationally while a parallel feasibility study examines local extraction from Kenyan maize gluten — a capability that would itself be a regional first.
• Dosage-form translation (capsules, paediatric-appropriate suspension, TB-04) targets formulation and filling with Kenyan pharmaceutical manufacturers rather than export for finishing.
• The regulatory pathway is planned Kenya-first: dossier submission through the Pharmacy and Poisons Board ahead of other markets.
• Analytical method validation, quality documentation and trained staff remain in Kenya after the grant, hosted with the Kenyan partners named in Section 16.

All financial decisions will follow the selected funder’s procurement and anti-corruption requirements. Suspected misconduct will be documented, escalated through an independent route and protected from retaliation.

The initial laboratory programme does not involve patient treatment. Required institutional, biosafety, material-transfer and research approvals will nevertheless be obtained before relevant work begins. Any later animal or human study will require a separate protocol, independent ethical review, regulatory authorization and appropriate consent processes.

13.1 Data governance

• Assign unique identifiers to batches, samples, methods, instruments and analytical outputs.
• Maintain role-based access, version control, audit trails and protected backups.
• Retain raw data and protocol deviations according to agreed institutional and regulatory schedules.
• Define ownership, permitted use, publication rights and return or destruction obligations in partner agreements.
• Share enabling technical information only through authorised, recorded channels.

13.2 Responsible scientific communication

Outputs will distinguish measured results, interpretation and future hypotheses. LSLP CREST will not state that the candidate reduces liver injury, improves adherence or produces clinical benefit unless appropriate studies demonstrate those outcomes.

Lead applicant: LSLP CREST Inc. (United States)
Project lead: Lumumba, Founder / Project Lead
Implementation partner: HENIKE Consultants Limited (Kenya)
Implementation location: Kenya
Contact details: [TO BE CONFIRMED]

Specialist pharmaceutical capabilities below are delivered through contracted facilities and named experts. HENIKE Consultants Limited — a private company registered in Kenya in 2019, specialising in health research, institutional capacity building, monitoring, evaluation, accountability and learning (MEAL), quality-of-care improvement and supply-chain consultancy — provides the programme's governance, analysis and field infrastructure. Bench formulation and analytical work remain contracted to a named laboratory before submission.

14.1 Institutional evidence required

Before submission, add LSLP CREST’s legal status, governance, financial controls, relevant project history, facilities, audited information and letters confirming access to specialist laboratories. No institutional capability should be claimed without documentary support.

LSLP CREST operates as a two-entity programme: LSLP CREST Inc. (United States) holds the intellectual property, funding relationships and regulatory strategy, while LSLP CREST Kenya is the implementation partner for bench work and the regional manufacturing pathway. LSLP CREST will remain accountable for programme strategy, protected know-how, funder reporting and integrated decision-making. Specialist research, testing and manufacturing work may be delivered by contracted or collaborating institutions only after scope, confidentiality, data ownership, material transfer and publication rights are agreed in writing.

Kenya-first by design

The origin story is Kenyan and stays Kenyan: the formulation concept was conceived in Nairobi, the specialist laboratory is Kenyan (KEMRI), the implementation partner is Kenyan (HENIKE), the manufacturing pathway is Kenyan, and the first regulatory filing is planned for Kenya through the Pharmacy and Poisons Board. The United States registration of LSLP CREST Inc. exists for a single purpose — funding eligibility under the SBIR/STTR rules — and the shareholding that satisfies those rules. Scientific credit, capacity building and the regional market remain Kenyan.

Naming the laboratory partner

Specialist bench and analytical work is planned with the Kenya Medical Research Institute (KEMRI), Kenya's national body for human-health research, which operates a dedicated Centre for Clinical Research for drug-development studies. KEMRI is named as the identified specialist laboratory for this programme; engagement is at the outreach and scoping stage and a written collaboration agreement must be executed before any submission names KEMRI as a contracted partner.

Dissemination will balance scientific transparency, public-interest responsibility and protection of legitimate intellectual property. Every output will pass through scientific, regulatory and IP review before release.

• Confidential technical reports for LSLP CREST, funders and authorised research partners.
• A non-confidential proof-of-concept summary describing the question, methods and bounded findings without enabling reproduction.
• Stakeholder briefings for TB-programme, regulatory, manufacturing and patient representatives where relevant.
• Peer-reviewed publication after protection decisions, partner review and removal of enabling details where necessary.
• A controlled investor data room for qualified diligence under confidentiality protections.
• A claims register linking each public statement to the evidence that supports it.

LSLP CREST proposes a bounded proof of concept that converts a scientifically plausible delivery hypothesis into a series of measurable decisions. Funding will not be used to market an assumed solution. It will be used to determine whether a reproducible candidate exists, whether its laboratory performance is meaningful, whether biological activity is retained and whether further nonclinical investment is justified.

Submission completion checklist

• Insert the funder and reproduce its criteria accurately.
• Confirm duration, requested amount and co-financing assumptions.
• Attach named team biographies and institutional evidence.
• Secure partner letters and define scopes of work.
• Complete literature references and source every quantitative claim.
• Obtain regulatory, ethics, IP and quality review.
• Approve a final confidential annex for authorised diligence only.

This section describes, trial by trial, how the laboratory work will be executed once the partnership with the Kenya Medical Research Institute (KEMRI) is formalised. It is written so that a reviewer can see exactly who does what, in what order, and how the data produced at the bench reaches the institute for independent verification. KEMRI's Centre for Clinical Research houses the drug-development and formulation capability this programme requires; the institute is identified as the specialist laboratory partner, with contact established at director@kemri.go.ke and +254 722 205 901 / +254 709 295 300 (P.O. Box 54840-00200, Nairobi, off Raila Odinga Way).

19.1 Roles at the bench

19.2 Standing trial routine

Every trial follows the same cycle regardless of scale, so a reviewer can trace any reported number back to a batch, an instrument and a dated entry.

1. Batch request and materials — LSLP CREST issues the batch protocol with quantities and settings; KEMRI confirms reagent inventory and instrument availability before the run is booked.
2. Formulation run at the contracted bench — The batch is prepared under a documented batch record; every reading is entered in the bench logbook at the time of measurement and raw traces are retained.
3. Characterisation — Particle size and PDI by dynamic light scattering, encapsulation by a validated HPLC method, and dissolution at pH 1.2 (stomach) and pH 7.4 (intestine).
4. Gate decision — Each batch is judged against the five acceptance gates — 150–220 nm, PDI ≤ 0.25, encapsulation above 80 %, less than 15 % released at 2 h, at least 85 % released at 24 h. Failed batches are recorded, not discarded.
5. Data pack submission — After each trial step, a numbered pack (reference format LSLP-TB0x-date-code) is submitted to KEMRI containing every batch reading and its pass/fail outcome, with a declaration that raw traces are held by LSLP CREST and available on request.
6. Independent verification — KEMRI re-measures an agreed subset of each batch and countersigns the characterisation record. Any discrepancy triggers a joint investigation before the next trial proceeds.

19.3 Acceptance gates used throughout

Every trial in this programme is judged against the same five gates. They are the identical thresholds enforced in the bench logbook, so a number recorded at the bench, a number in a data pack to KEMRI and a number in a funder report cannot diverge.

A batch that fails any gate is recorded as failed and carried forward in the data pack. Failed batches are evidence, not waste, and the programme reports them.

19.4 Equipment schedule

Equipment is split between what LSLP CREST expects to access under the KEMRI contract and what must be booked, hired or purchased. Availability is confirmed before each trial is booked.

19.5 Reagents and materials

LSLP CREST supplies no live cultures. All biological material is sourced, held and destroyed by KEMRI under its own procedures.

19.6 Trial-by-trial method and timeline

Each trial below states the objective, the method as it will be performed at the bench, how long it takes and the decision that closes it. All five gates in 19.3 apply to every characterised batch.

TB-01 — Independent confirmation of the lead formulation

TB-02 — Condition screen and lead selection

TB-03 — Reproducibility, dual drug and biology

TB-04 — Scale-up and dosage-form translation

19.7 Data chain of custody

• Every reading is entered in the bench logbook at the time of measurement, tagged with trial, batch label and notes.
• Each submission to KEMRI carries a unique reference and the full pass/fail gate record; nothing is summarised away — failed batches ship too.
• Raw instrument traces, weighing records and chromatograms remain with LSLP CREST and are available to KEMRI and the funder on request.
• KEMRI's countersigned re-measurements become the reference values carried into the next milestone and into the funder's reports.

19.8 Quality, safety and compliance

• Characterisation methods are validated at KEMRI before milestone M2 closes: a validated HPLC encapsulation assay, dissolution mass balance and stability-indicating methods.
• Method validation covers specificity, linearity, accuracy, precision, limits of detection and quantification, and solution stability, with acceptance criteria agreed in advance.
• Mycobacterial work is performed only in KEMRI's appropriately contained laboratories under its own biosafety procedures; LSLP CREST supplies no live cultures.
• No clinical or safety claim is made before the hepatocyte endpoint is measured, and no result leaves the programme outside the agreed governance.
• All work is documented to a good-laboratory-practice standard: batch records, instrument logs, calibration certificates, personnel training records and a controlled document register.

This section is the grant-seeking summary: what LSLP CREST is asking for, what the money buys, when each result lands, and why this programme is a credible fit for a tuberculosis research or product-development grant. Costs are indicative planning figures in US dollars, built from Kenyan laboratory rates, and will be replaced with quotation-backed numbers once the contracted facilities are named. The trial-by-trial laboratory delivery protocol with KEMRI is set out in Section 19.

20.1 The ask

LSLP CREST is structured as a two-entity programme. LSLP CREST Inc. is a registered United States company that owns the intellectual property and applies for funding. LSLP CREST Kenya is the implementation partner: it runs the bench programme and holds the regional manufacturing pathway. This structure was chosen deliberately — it makes the programme eligible for United States small-business innovation funding while keeping the scientific work, capacity building and eventual manufacturing in Kenya.

20.2 Corporate structure and funding route

The primary route is the NIH Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programme. These awards are open only to United States small business concerns — which is what LSLP CREST Inc. is. A Phase I award (approximately USD 300,000 over 6–12 months) funds the feasibility work covered by milestones M1–M3 below; a Phase II award (approximately USD 2 million over up to two years) funds the full nonclinical package, M4–M8. The USD 485,000 programme cost in this section therefore sits between a Phase I and a Phase II and can be financed either as a scoped Phase I with bridge funding, or from the alternate instruments listed in 20.1.

Work performed in Kenya is permitted under SBIR/STTR as subcontracted effort, and it must be disclosed. NIH's foreign disclosure and risk-management rules — tightened by the SBIR and Economic Security Act of April 2026 — require the applicant to identify every foreign entity performing substantive work, what that work is, and the data and intellectual-property arrangements. LSLP CREST discloses all of this openly: the Kenyan partner is named in the proposal, operates under a written contract, and does not hold the IP. This is a disclosure obligation, not a prohibition, and the structure above is designed to satisfy it.

20.3 Indicative budget

Two-thirds of the request is laboratory work and the evidence it produces. No part of the budget funds marketing, and no claim of clinical benefit is financed before the toxicity endpoint is measured.

20.4 Milestones and timeline

20.5 Why LSLP CREST fits a TB grant

20.6 What the funder receives

• Quarterly technical reports with batch-level data, not summaries alone.
• Access to the trial record behind every reported number, including failed batches.
• An independent advisory review at milestones 3, 6 and 8.
• A final evidence package sufficient for a third party to judge whether nonclinical development is justified.
• Publication of the methods and outcomes, including negative results.